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

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

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28-03-2013 дата публикации

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

Номер: US20130079525A1
Автор: MORI Kohei, NISHIYAMA Akira, NOJIRI Masutoshi, TAOKA Naoaki
Принадлежит: KANEKA CORPORATION

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing. 118.-. (canceled) The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate, and to intermediates useful for producing the 3-aminopiperidine.As methods for producing an optically active 3-aminopiperidine or salt thereof, or a derivative of optically active 3-aminopiperidine, for example, the following methods are known:1) a method, wherein L-ornithine monohydrochloride is methyl-esterified, and then (S)-3-amino piperidone is obtained by chromatography with an ion exchange resin, the (S)-3-amino piperidone is reacted with lithium aluminum hydride to be (S)-3-aminopiperidine, an inorganic salt is removed by filtration, and the target compound is purified (Non-patent Document 1);2) a method, wherein ethyl nipecotate is optically resolved using L-tartaric acid, the nitrogen atom is protected with benzyloxycarbonyl group, the ethyl ester is hydrolyzed in alkaline condition, Curtius rearrangement is carried out using ...

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Номер записи: 1
04-04-2013 дата публикации

NITROGENOUS HETEROCYCLIC DERIVATIVE AND MEDICINE CONTAINING THE SAME AS AN ACTIVE INGREDIENT

Номер: US20130085275A1
Автор: NISHIZAWA Rena, SHIBAYAMA Shiro, TAKAOKA Yoshikazu
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

A compound represented by formula (I), a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof: 133-. (canceled)34. A compound selected from the group consisting of(1) N-[6-(4-{[4-(butyl{[(2,4-difluorophenyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)-3-pyridinyl]methanesulfonamide,(3) N-{4-[4-({4-[{[(2-hydroxybutyl)amino]carbonyl}(phenyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide,(4) N-{4-[4-({4-[butyl({[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}carbonyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide,(5) 5-[({butyl[1-(4-{4-[(methylsulfonyl)amino]phenoxy}benzyl)-4-piperidinyl]amino}carbonyl)amino]-2,4-difluoro-N-methylbenzamide,(6) N-{4-[4-({4-[{[(4-hydroxycyclohexyl)amino]carbonyl}(phenyl)amino]-1-piperidinyl}methyl)phenoxy]phenyl}methanesulfonamide,(7) N-[4-(4-{[4-(3-butenyl {[(2-hydroxybutyl)amino]carbonyl}amino)-1-piperidinyl]methyl}phenoxy)phenyl]methanesulfonamide,(8) N-butyl-N′-(2,4-difluorophenyl)-N-(1-{4-[4-(4-morpholinylsulfonyl)phenoxy]benzyl}-4-piperidinyl)urea,(9) N-butyl-2-(2,4-difluorophenyl)-N-[1-(4-{4-[(methylsulfonyl)amino]phenoxy}benzyl)-4-piperidinyl]acetamide,(10) N-{4-[(5-{[4-(butyl{[(1-methyl-1H-pyrazol-4-yl)amino]carbonyl}amino)-1-piperidinyl]methyl}-2-pyridinyl)oxy]phenyl}methanesulfonamide,(11) N-(4-{4-[(4-{{[(4-fluorophenyl)amino]carbonyl}[4-(methylsulfanyl)phenyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide,(12) N-(4-{4-[(4-{{[(4-fluorophenyl)amino]carbonyl}[3-(methylsulfanyl)phenyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide,(13) N-butyl-2,4-difluoro-N-[1-(4-{4-[(methylsulfonyl)amino]phenoxy}benzyl)-4-piperidinyl]benzamide,(14) N-(4-{4-[(4-{{[(4-fluorophenyl)amino]carbonyl}[4-(methylsulfinyl)phenyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide,(15) N-(4-{4-[(4-{{[(4-fluorophenyl)amino]carbonyl}[3-(methylsulfinyl)phenyl]amino}-1-piperidinyl)methyl]phenoxy}phenyl)methanesulfonamide,(16) N-(4-{4-[(4-{{[(4-fluorophenyl)amino] ...

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Номер записи: 2
16-05-2013 дата публикации

DIAMINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE A4 HYDROLASE

Номер: US20130123243A1
Автор: Arnaiz Damian O., Brown Greg, Claret Emmanuel, Cleve Arwed, Davey David, Guilford William, Khim Seok-Kyu, Kirkland Thomas, Kochanny Monica J., Liang Amy, Light David, Parkinson John, Vogel David, Wei Guo Ping, Ye Bin
Принадлежит:

This invention is directed to compounds of formula (I): 3. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, cyano, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each independently hydrogen or halo.'}4. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, optionally substituted phenyl, furanyl, thienyl, thiazolyl, or optionally substituted oxazolyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each hydrogen.'}6. A compound according to wherein R an optionally substituted heteroaryl.7. A compound according to wherein R is furanyl claim 6 , oxazoyl claim 6 , pyrazolyl claim 6 , pyridinyl claim 6 , triazolyl claim 6 , thiazolyl claim 6 , or benzothiazolyl claim 6 , each of which is optionally substituted.8. A compound according to wherein:{'sup': 2', '7', '5a', '5b', '5c, 'Rand R, together with the nitrogens to which they are attached and one of R, Rand R, form an optionally substituted 6- to 10-membered bridged N-heterocyclyl.'}10. A compound according to wherein:{'sup': 3', '12', '12', '12, 'Ris a direct bond, —O—, —R—O—, —O—R—, —O—R—O—, or an optionally substituted straight or branched alkylene chain;'}{'sup': 4', '12a, 'Ris a direct bond, —O—R— or an optionally substituted straight or branched alkylene chain;'}{'sup': 8', '13', '10', '13', '10', '13', '10', '11, 'Ris aralkyl optionally substituted with one or more substituents selected from the group consisting of —R—OR, —R—C(═O)ORand —R—C(═O)N(R)R;'}{'sup': 9', '10, 'each Ris independently alkyl, halo or —O—R;'}{'sup': '12', 'Ris an optionally substituted straight ...

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Номер записи: 3
30-05-2013 дата публикации

CONFORMATIONALLY RESTRICTED UREA INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE

Номер: US20130137726A1
Автор: Gless, Hammock Bruce D., Huang Huazhang, Jones Paul D., JR. Richard, Morisseau Christophe, Tsai Hsing-Ju
Принадлежит: The Regents of the University of California

Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases. 3. The method in accordance with or , wherein Ris adamantyl.4. The method in accordance with or , wherein Ris cycloheptyl or cyclohexyl.5. The method in accordance with or , wherein L is a —C(O)—.6. The method in accordance with or , wherein Ris selected from the group consisting of hydrogen , C-Calkyl , and arylC-Calkyl.7. The method in accordance with or , wherein Ris C—Calkyl.8. A method in accordance with claim 2 , wherein said compound is selected from the group consisting of:N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-propionylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-butyrylpiperidine-4-yl)-N′-(adamant-1-yl)urea;N-(1-benzoyl piperidin-4-yl)-N′-(adamant-1-yl)urea;4-[4-(3-adamantan-1-yl-ureido)-piperidin-1-yl]-4-oxo-butanoic acid methyl ester;5-[4-(3-adamantan-1-yl-ureido)-piperidin-1-yl]-5-oxo-pentanoic acid methyl ester;2-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;3-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;4-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;1-(1-acetyl-piperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea;1-(1-trifluoromethylcarbonylpiperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea; and1-(1-acetyl-piperidin-4-yl)-3-cycloheptyl)urea;or a pharmaceutically acceptable salt thereof.9. The method in accordance with claim 8 , wherein said compound is selected from the group consisting of:N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-propionylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-butyrylpiperidine-4-yl)-N′-(adamant-1-yl)urea; andN-(1-benzoylpiperidin-4-yl)-N′-(adamant-1-yl)ureaor a pharmaceutically acceptable salt thereof.10. The method in accordance with claim 8 , wherein said compound is N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea or a pharmaceutically acceptable salt thereof.11. ...

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Номер записи: 4
06-06-2013 дата публикации

ACYL PIPERIDINE INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE

Номер: US20130143925A1
Автор: Hammock Bruce D., Lee Kin Sing, Morisseau Christophe, Rose Tristan
Принадлежит: The Regents of the University of California

Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases. 125.-. (canceled)26. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.27. A method for inhibiting a soluble epoxide hydrolase claim 29 , the method comprising contacting the soluble epoxide hydrolase with an amount of a compound of sufficient to inhibit the soluble epoxide hydrolase.28. A method for monitoring the activity of a soluble epoxide hydrolase claim 29 , the method comprising contacting the soluble epoxide hydrolase with an amount of a compound of sufficient to produce a detectable change in the fluorescence of the soluble epoxide hydrolase by interacting with one or more tryptophan residues present in the catalytic site of said sEH.29. A compound is selected from the group consisting of1-(4-Methoxyphenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Phenoxyphenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Fluorophenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Chlorophenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Iodophenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(3,5-Dichlorophenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(4-Perfluoroisopropylphenyl)-3-(1-propionylpiperidin-4-yl)urea,1-(1-cyclopropanecarbonylpiperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea,1-(1-(2-methylbutyryl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea,1-(1-(3,3,3-trifluoropropionyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea,1-(1-(4,4,4-trifluorobutyryl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea,1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea,1-(1-(Cyclopropanecarbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea,1-(1-(Trifluoroacetyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea,1-(1-(propylsulfonyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea,1-(1-(butylsulfonyl)piperidin-4-yl)-3-(4-( ...

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Номер записи: 5
06-06-2013 дата публикации

BENZAMIDE DERIVATIVES AND THEIR USE AS HSP90 INHIBTORS

Номер: US20130143926A1
Автор: Donald Alastair David Graham, McDermott Joanne, Moffat David Festus Charles, Patel Sanjay Ratilal
Принадлежит:

The invention provides a compound which is (a) a phenylamide derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate, prodrug or solvate thereof: wherein R, R, R, R, R, Rand Rare as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90. 2. A compound as claimed in wherein Ris hydroxy.3. A compound as claimed in wherein R claim 1 , R claim 1 , Rand Rare the same or different and represent hydrogen or halogen atoms or hydroxy claim 1 , unsubstituted Calkyl or unsubstituted Calkoxy groups.4. A compound as claimed in wherein either:{'sup': 6', '7', '8', '9', '8', '9, 'sub': 3', '1-4', '1-4, '(i) Rrepresents —CH, Rrepresents —CRR-A wherein Rand Rare the same or different and represent a hydrogen or halogen atom or an unsubstituted Calkyl or Calkoxy group, and A represents a phenyl ring substituted with a group W; or'}{'sup': 6', '7, 'sub': 1-4', '1-4', '1-4', '1-4', '1-4', '1-2, '(ii) Rand R, together with the nitrogen atom to which they are bonded, form a pyrrolidinyl, piperidinyl or isoindolinyl group which is substituted with a group W and is optionally further substituted with 1 or 2 groups which are the same or different and are selected from halogen atoms and unsubstituted Calkyl, Calkoxy, hydroxyl, Chaloalkyl, Chaloalkoxy, Chydroxyalkyl, cyano, nitro, —SR′ and —NR′R″ groups where R′ and R″ are the same or different and represent hydrogen or unsubstituted Calkyl.'}5. A compound as claimed in wherein Alkrepresents a bond claim 1 , an unsubstituted Calkylene group claim 1 , or an unsubstituted —(Calkylene)-NH—(Calkylene)- group.6. A compound as claimed in wherein either:{'sup': 12', '13, 'sub': 1-6', '3-7', '6-10', '1-4', '6-10', '1-4', '3-7, '(i) Rand Rare the same or different and represent hydrogen, Calkyl, Ccarbocyclyl, Caryl, —(Calkyl)-(Caryl), or —(Calkyl)-(Ccarbocyclyl); or'}{'sup': 12', '13, 'sub': '3-7', '(ii) Rand R, together with the carbon atom to which they are bonded, ...

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Номер записи: 6
04-07-2013 дата публикации

5-HT2B RECEPTOR ANTAGONISTS

Номер: US20130172386A1
Автор: Thuring Johannes Wilhelmus John F., VER DONCK Luc August Laurentius
Принадлежит: Janssen Pharmaceutica, NV

The present invention relates to novel fluorinated piperidine derivatives having antagonistic activity at the 5-HTreceptor, pharmaceutical compositions comprising these compounds and their use as a medicine. 2. The compound according to wherein R is fluoro and the compound is a racemic mixture claim 1 , or an addition salt or a solvate thereof.3. The compound according to wherein R is fluoro and the compound has an optical rotation [ ]=−14.4° (c=0.3 claim 1 , MeOH claim 1 , λ=598 nm; 20° C.) claim 1 , or an addition salt or a solvate thereof.4. A pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in and a pharmaceutically acceptable carrier.5. A process for preparing a pharmaceutical composition as defined in claim 1 , characterized in that a pharmaceutically acceptable carrier is intimately mixed with a therapeutic ally effective amount of a compound as defined in .6. A compound as defined in for use in the treatment or prevention of pulmonary arterial hypertension claim 1 , pulmonary fibrosis or irritable bowel syndrome.7. A method of treating or preventing pulmonary arterial hypertension claims 1 , pulmonary fibrosis or irritable bowel syndrome claims 1 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound as defined in . The present invention relates to novel fluorinated piperidine derivatives having antagonistic activity at the 5-HTreceptor, pharmaceutical compositions comprising these compounds and their use as a medicine.Cisapride is a serotonin 5-HTreceptor agonist useful as a gastroprokinetic drug. It interacts significantly with several other receptors such as 5-HTand 5-HT; D; 5-HT; Alpha, Alpha, Alphaand Alpha. It was withdrawn from some markets in 2000 due to reports of sudden cardiac arrhythmias. At the origin of this side effect is drug-induced QT prolongation by blockade of the hERG potassium channel (human ether-a-go-go related gene). One of ...

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Номер записи: 7
05-09-2013 дата публикации

SMALL MOLECULE INHIBITORS OF EBOLA AND LASSA FEVER VIRUSES AND METHODS OF USE

Номер: US20130231332A1
Автор: Chandran Kartik, Cunningham James, Lee Kyungae, Ren Tao
Принадлежит:

The present invention relates to compositions and methods for the treatment of infection by enveloped viruses, such as Ebola and Lassa fever viruses. 1. (canceled)3. (canceled)5. (canceled)9. The method of claim 7 , wherein the viral infection is an Ebola infection.10. The method of claim 7 , wherein the viral infection is a Lassa fever infection. This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/379,138, filed Sep. 1, 2010, the contents of which are hereby incorporated by reference.This invention was made with government support under AI057159 awarded by the National Institutes of Health. The government has certain rights in the invention.Ebolaviruses (EboV) are enveloped negative-sense RNA viruses that cause sporadic outbreaks of rapidly fatal zoonotic infection. EboV is transmitted by close contact and virus levels increase by 75-fold/day for several days after initial infection. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines, including interferon-α and TNF-α in response to infection. The endothelial cell dysfunction associated with “cytokine storm” results in capillary leak, hypovolemic shock, disseminated intravascular coagulation and inadequate perfusion of major organs. In many outbreaks, the mortality rate from EboV infection exceeds 75% in 14 days. Current therapy is supportive; there is no effective anti-EboV vaccine or therapy. The unpredictable onset, ease of transmission, rapidity of progression, high mortality, and bio-terrorism potential have created a high level of public concern about EboV. Therefore, development of anti-EboV drugs is a high priority.Recent studies have identified promising drug targets. Previously, it was found that stepwise proteolytic cleavage of EboV envelope glycoprotein GP by the lysosomal cysteine proteases cathepsin L (Cat L) and cathepsin B (Cat B) is required for infection; and therefore, inhibitors of Cat L and Cat B are ...

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Номер записи: 8
03-10-2013 дата публикации

CALCIUM-SENSING RECEPTOR-ACTIVE COMPOUNDS

Номер: US20130261132A1
Автор: BlÆher Lars Kristian Albert, Vedsø Per
Принадлежит: LEO PHARMA A/S

Compounds of general formula (I), their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, and methods of treating diseases with said compounds. 3. A compound according to claim 1 , wherein Ar represents phenyl or naphthyl claim 1 , optionally substituted with one or two claim 1 , same or different substituents selected from halogen or Calkoxy.4. A compound according to claim 3 , wherein phenyl is substituted with one or two claim 3 , same or different substituents selected from chloro claim 3 , fluoro or methoxy.5. A compound according to claim 4 , wherein Ar represents 4-fluoro-3-methoxy or 3-chlorophenyl.6. A compound according to claim 1 , wherein Ar represents naphthyl.7. A compound according to claim 1 , wherein Rrepresents Calkenyl claim 1 , hydroxyCalkyl claim 1 , hydroxyCalkylaminoCalkyl claim 1 , Calkyl sulfonyl amino Calkyl claim 1 , aminosulfonylCalkyl claim 1 , aminocarbonylCalkyl claim 1 , or Cheterocycloalkyl comprising 1-2 hetero atoms selected from N claim 1 , O and S.8. A compound according to claim 7 , wherein Rrepresents hydroxyCalkylaminoCalkyl claim 7 , Calkyl sulfonylaminoCalkyl claim 7 , amino sulfonylCalkyl claim 7 , amino carbonyl Calkyl claim 7 , or Cheterocycloalkyl comprising 1-2 hetero atoms selected from N and O.9. A compound according to claim 1 , wherein Rrepresents hydrogen.10. A compound according claim 1 , wherein Rand Rtogether with the nitrogen to which they are attached form a 6 membered Cheterocycloalkyl comprising one or two nitrogen atom(s) claim 1 , said heterocyclic ring being optionally substituted with oxo claim 1 , —S(O)NH claim 1 , Calkylcarbonyl claim 1 , or hydroxyCalkyl.11. A compound according to claim 10 , wherein the heterocyclic ring is selected from the group consisting of piperazinyl or piperidyl claim 10 , ...

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Номер записи: 9
17-10-2013 дата публикации

BETA-LACTAMASE INHIBITORS

Номер: US20130274475A1
Автор: Mangion Ian, Rivera Nelo, Ruck Rebecca T., Shelvin Michael
Принадлежит:

Substituted bicyclic beta-lactams of Formula I: 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein bond a is a single bond and X is —CH— or —CHCH—.3. The compound according to or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OSOM.4. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris OSOH.5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C(O)N(R)R.6. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetA claim 5 , CH-HetA claim 5 , CHCH-HetA claim 5 , CH(CH)-HetA claim 5 , or CH(CHOH)-HetA.7. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein HetA is an optionally fused claim 6 , saturated heterocyclic ring selected from the group consisting of azetidinyl claim 6 , pyrrolidinyl claim 6 , oxopyrrolidinyl claim 6 , piperidinyl claim 6 , piperazinyl claim 6 , tetrahydropyranyl claim 6 , tetrahydrothiopyranyl claim 6 , morpholinyl claim 6 , 1 claim 6 ,1-dioxidotetrahydrothiopyranyl claim 6 , azepanyl claim 6 , oxazepanyl claim 6 , azocanyl claim 6 , and azabicyclo[3.1.0]cyclohexyl claim 6 , wherein the heterocyclic is optionally substituted with 1 or 2 (CH)N(R)Rand optionally substituted with 1 or 2 (CH)R.9. The compound according to claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein T is H claim 8 , CH claim 8 , pyrrolidin-3-yl claim 8 , piperidin-4-yl claim 8 , (CH)OCH claim 8 , (CH)OH claim 8 , (CH)F claim 8 , (CH)-piperidinyl claim 8 , (CH)-pyrrolidinyl; and T′ is H claim 8 , F claim 8 , O—Calkyl claim 8 , OH claim 8 , NH claim 8 , N(H)CH claim 8 , N(CH).10. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetB.11. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof ...

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Номер записи: 10
17-10-2013 дата публикации

CONFORMATIONALLY RESTRICTED UREA INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE

Номер: US20130274476A1
Автор: Gless, Hammock Bruce D., Huang Huazhang, Jones Paul D., JR. Richard, Morisseau Christophe, Tsai Hsing-Ju
Принадлежит:

Inhibitors of the soluble epoxide exemplary hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases. 120.-. (canceled)2212. The compound of claim 21 , wherein Ris phenyl claim 21 , optionally substituted with from to substituents each independently selected from the group consisting of C-Chaloalkyl and C-Chaloalkoxy.23. The compound of claim 21 , wherein Ris selected from the group consisting of C-Calkyl and C-Ccycloalkyl.24. The compound of claim 21 , wherein Ris C-Calkyl.25. The compound of claim 21 , wherein Ris C-Ccycloalkyl.26. The compound of claim 21 , wherein Ris haloC-Calkyl.27. The compound of claim 21 , selected from the group consisting of:1-(1-acetyl-piperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea; and1-(1-trifluoromethylcarbonylpiperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea; or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. patent application Ser. No. 13/455,861, filed Apr. 25, 2012, which is a divisional of U.S. patent application Ser. No. 11/685,674, filed Mar. 13, 2007, which claims the benefit of U.S. Provisional Patent Application No. 60/782,172, filed Mar. 13, 2006, each of which is incorporated by reference herein in its entirety.The U.S. Government as certain rights to the invention pursuant to contract ES02710 & HL078096 awarded by the National Institutes of Health.Epoxide hydrolases (EHs, EC 3.3.2.3) catalyze the hydrolysis of expoxides or arene oxides to their corresponding diols by the addition of water (see, Oesch, F., et al., 1973, 3, 305-340). Some EHs play an important role in the metabolism of a variety of compounds including hormones, chemotherapeutic drugs, carcinogens, environmental pollutants, mycotoxins and other harmful foreign compounds.There are two well-studied EHs, microsomal epoxide hydrolase (mEH) and soluble epoxide hydrolase (sEH). These enzymes are very distantly related, have different subcellular localization, and have ...

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Номер записи: 11
24-10-2013 дата публикации

Methods For Preparing Fentanyl And Fentanyl Intermediates

Номер: US20130281702A1
Автор: LePine Anthony J., Pease Jonathan P., Smith Catherine M.
Принадлежит:

A method and an intermediate are provided for preparing fentanyl. Aniline and 1-phenylethyl-4-piperidone are reacted with a borane complex, in a lower C-Calcoholic solvent, in the presence of an alkanoic acid. The reaction mixture is then treated with a hydrohalic acid to precipitate 4-anilino-N-phenethyl-4-piperidine (ANPP) as the bis-hydrohalide salt in high yield and purity. This ANPP salt may be directly treated with propionyl halide to produce fentanyl, or the ANPP salt may be converted to the free base of ANPP and similarly treated with propionyl halide to produce fentanyl. 2. The method of wherein:D is heterocyclic.3. The method of wherein:the electron donor atom is selected from nitrogen, oxygen, or sulfur.4. The method of wherein:the electron donor atom is nitrogen.5. The method of wherein R claim 1 , R claim 1 , and Rare hydrogen.6. The method of wherein:D is selected from substituted or unsubstituted pyridine, substituted or unsubstituted aniline, or substituted or unsubstituted amine.7. The method of wherein:D is 5-ethyl-2-methylpyridine, and{'sub': 1', '2', '3, 'R, R, and Rare hydrogen.'}8. The method of further comprising:{'sub': 1', '4, 'adding a C-Calcoholic solvent in step (b).'}9. The method of further comprising:adding an organic acid in step (b).10. The method of wherein:{'sub': 1', '8, 'the organic acid is an alkanoic acid of C-C.'}11. The method of wherein:the organic acid is acetic acid.12. The method of further comprising:(c) adding a mineral acid at completion of reaction thereby crystallizing out a salt of the compound of formula (II).13. The method of wherein:the mineral acid is a hydrohalic acid.14. The method of wherein:the mineral acid is hydrochloric acid.17. The method of wherein the mineral acid is a hydrohalic acid.18. The method of wherein:the propionyl halide is propionyl chloride.19. The method of wherein:D is heterocyclic, and the electron donor atom is nitrogen.20. The method of wherein:D is selected from substituted or ...

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Номер записи: 12
21-11-2013 дата публикации

MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

Номер: US20130310379A1
Автор: Albrecht Brian K., Audia James Edmund, GAGNON Alexandre, Harmange Jean-Christophe, Naveschuk Christopher G.
Принадлежит: CONSTELLATION PHARMACEUTICALS

Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein. 224-. (canceled)26. The compound of claim 25 , wherein R claim 25 , R claim 25 , Rand R are methyl.27. The compound of claim 26 , wherein R claim 26 , R claim 26 , R claim 26 , R claim 26 , Rand R′ are hydrogen.28. The compound of claim 26 , wherein Lis selected from —OCH— claim 26 , —CHO— claim 26 , —OC(O)— claim 26 , —N(R′)C(O)— claim 26 , —C(O)N(R′)— claim 26 , and optionally substituted ethenylene.2930.-. (canceled)31. The compound of claim 28 , wherein Lis —NH—C(O)— claim 28 , —OCH— claim 28 , —CHO— claim 28 , —OC(O)— claim 28 , and —CH═CH—.32. The compound of claim 25 , wherein Ring B is optionally substituted phenyl or optionally substituted pyridinyl.3336.-. (canceled)37. The compound of claim 32 , wherein Lis selected from —CHO— claim 32 , —O— claim 32 , and —CH(CH)O.38. The compound of claim 25 , wherein Ring C is optionally substituted phenyl.3940.-. (canceled)41. The compound of claim 25 , wherein Ring C is optionally substituted pyridinyl claim 25 , pyrimidinyl or pyrazinyl.43. (canceled)44. The compound of claim 25 , wherein Ring C is selected from the group consisting of cyclopropyl claim 25 , cyclobutyl claim 25 , cyclopentyl claim 25 , cyclohexyl and cycloheptyl.45. (canceled)46. The compound of claim 25 , wherein Ring C is selected from pyrrolidinyl claim 25 , furanyl claim 25 , pyrazolidinyl claim 25 , imidazolidinyl claim 25 , thiazolidinyl claim 25 , piperidinyl claim 25 , piperazinyl and morpholinyl.47. (canceled)48. The compound of claim 25 , wherein Ring C is optionally substituted indolyl claim 25 , quinolinyl claim 25 , isoquinolinyl or naphthyl.49. (canceled)50. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.5156-. (canceled) The present application claims priority to U.S. Provisional Application No. 61/415,713, filed Nov. 19, 2011, the entire contents of which are hereby incorporated herein ...

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Номер записи: 13
02-01-2014 дата публикации

ANDROGEN RECEPTOR MODULATOR COMPOUNDS AND METHODS

Номер: US20140005186A1
Автор: Chen Jyun-Hung, HIGUCHI Robert I., Kallel E. Adam, Lau Thomas Lot Stevens, Miller Todd A., Pedram Bijan, Ruppar Daniel A., Van Oeveren Cornelis Arjan, Zhi Lin
Принадлежит: Ligand Pharmaceuticals Incorporated

Provided herein are compounds having a structure selected from among Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V) and Formula (VI) that are androgen receptor modulators and/or androgen receptor binding agents. Also disclosed are methods of making and using such compounds, including, but not limited to, using such compounds for treating various conditions. 2. The method of claim 1 , wherein the androgen receptor is in a cell.3. The method of claim 1 , wherein the compound is an androgen receptor agonist.4. The method of claim 1 , wherein the compound is an androgen receptor antagonist.5. The method of claim 1 , wherein the compound is a compound of Formula II claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , amide or prodrug thereof.6. The method of claim 1 , wherein the compound is selected from:N,N-bis(2,2,2-trifluoroethyl)-3-methyl-4-nitroaniline;N,N-bis(2,2,2-trifluoroethyl)-4-nitroaniline;4-Bromo-N,N-bis(2,2,2-trifluoroethyl)-3-(trifluoromethyl)aniline;4-(Bis(2,2,2-trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile;(5R)—N-(4-nitrophenyl)-5-(dimethyl-tort-butylsilyloxymethyl)-2-pyrrolidone;(5R)—N-(4-nitrophenyl)-5-(hydroxymethyl)-2-pyrrolidone;(2R)—N-(4-nitro-3-trifluoromethylphenyl)-2-(dimethyl-tert-butylsilyloxymethyl)pyrrolidine (compound 106);(2R)—N-(4-nitro-3-trifluoromethylphenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-formylpyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2R)—N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2S)—N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2R)—N-(4-nitrophenyl)-2-(R)-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine;(2S)—N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl);(2S)—N-(4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2- ...

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Номер записи: 14
23-01-2014 дата публикации

PROCESS AND INTERMEDIATES FOR THE SYNTHESIS OF 8-[-METHYL]-8-PHENYL-1,7-DIAZA-SPIRO[4.5]DECAN-2-ONE COMPOUNDS

Номер: US20140024834A1
Автор: Huttenloch Monika Erika, Mergelsberg Ingrid, Paliwal Sunil, Scherer Dominik Hermann, Shih Neng-Yang, Tsui Hon-Chung
Принадлежит: OPKO Health, Inc.

This application discloses a process to synthesize 8-({1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-pheny-1.7-diaza-spiro[4.5]decan-2-one comprising reacting a compound of the Formula 27a-sulfonate with zinc in the presence of acetic acid. 3. The process of wherein Ris selected from norbornyl and methyl.4. The process of any of and wherein the base is a basic alumina.5. The process of claim 3 , wherein the base is basic alumina having a Brockman activity of IV.8. The process of wherein claim 1 , Ris selected from methyl and isobornyl.9. The process of wherein Rmethyl.10. The process of wherein Ris selected from methyl claim 1 , (−)-8-phenylmenthyl claim 1 , isobornyl claim 1 , 1-adamantanyl claim 1 , 2-adamantanyl claim 1 , adamantane methanyl claim 1 , and (+)-isopinocamphenyl.11. The process of wherein Ris selected frommethyl, (−)-8-phenylmenthyl, isobornyl, 1-adamantanyl, 2-adamantanyl, adamantane methanyl, and (+)-isopinocamphenyl.12. The process of claim 6 , wherein Ris Cbz.13. The process of claim 12 , wherein Ris methyl.15. The composition of produced in accordance with the process of any of to . This application is based on and claims the priority of U.S. Provisional Application No. 60/919,666, filed Mar. 22, 2007, which is incorporated herein by reference in its entirety.This application discloses a novel process for the preparation of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds, which have utility, for example, as NK-1 receptor antagonist compounds, and intermediates useful in the synthesis thereof.Identification of any publication, patent, or patent application in this section or any section of this application is not an admission that such publication is prior art to the present invention.The preparation of diazaspirodecan-2-ones for example, 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, for example, (5S,8S)-8-[{(1R)-1-(3,5-Bis-( ...

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Номер записи: 15
20-02-2014 дата публикации

Novel Compositions for Inhibiting Virus Entry and Promoting Virolysis, and Methods Thereof

Номер: US20140050793A1
Автор: Bastian Arangassery Rosemary, Chaiken Irwin, Kantharaju , Papazoglou Elisabeth S.
Принадлежит: DREXEL UNIVERSITY

The present invention includes a composition comprising a gold nanoparticle complexed with a cysteine-containing peptide. The invention also includes the method of preparing a composition comprising a gold nanoparticle complexed with a cysteine-containing peptide. The invention further includes a method of causing virolysis of a virus using the compositions described therein. 2. The composition of claim 1 , wherein Pcomprises at least one cysteine residue.3. (canceled)4. (canceled)5. The composition of claim 1 , wherein Pis βA Gln βA Cys-NH claim 1 , wherein βA is beta-alanine.7. The composition of claim 1 , further comprising at least one gold nanoparticle claim 1 , wherein the at least one nanoparticle is complexed to the peptide of formula (I) through the at least one thiol group.8. (canceled)9. (canceled)10. The composition of claim 1 , further comprising at least one additional compound useful for treating viral infections.11. (canceled)12. The composition of claim 1 , wherein the peptide is encapsulated in a hydrogel.13. (canceled)14. (canceled)16. The composition of claim 15 , wherein Pcomprises at least one cysteine residue.17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. The composition of claim 15 , further comprising at least one additional compound useful for treating viral infections.22. (canceled)23. The composition of claim 15 , wherein the peptide is encapsulated in a hydrogel.24. (canceled)25. (canceled)27. (canceled)28. The method of claim 26 , wherein Pis βA Gln βA Cys-NH claim 26 , wherein βA is beta-alanine30. (canceled)32. The method of claim 31 , wherein the virus is HIV-1 claim 31 , influenza claim 31 , ebola or dengue.33. (canceled)34. (canceled)35. The method of claim 31 , wherein Pis βA Gln βA Cys-NH claim 31 , wherein βA is beta-alanine.37. (canceled)38. The method of claim 31 , wherein the mammal is further administered at least one additional compound useful for treating viral infections.39. (canceled)40. (canceled)41. The ...

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Номер записи: 16
06-03-2014 дата публикации

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

Номер: US20140066621A1
Автор: Bruncko Milan, Colman Peter Malcolm, Czabotar Peter Edward, Dai Yujia, Ding Hong, Doherty George A., Elmore Steven W., Hasvold Lisa, Hexamer Laura, Kunzer Aaron R., Lessene Guillaume Laurent, Mantei Robert A., McClellan William J., Park Chang H., Park Cheol-Min, PETROS ANDREW M., Song Xiahong, Souers Andrew J., Sullivan Gerard M., Tao Zhi-Fu, Wang Gary T., Wang Le, Wang Xilu, Wendt Michael D.
Принадлежит:

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein. 112-. (canceled)15. A compound or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2,3-difluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2,5-dichlorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;N-(4-((4-aminotetrahydro-2H-pyran-4-yl)methylamino)-3-nitrophenylsulfonyl)-2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(3-fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(2-chloro-4-fluorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2-fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(2-fluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1- ...

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Номер записи: 17
07-01-2016 дата публикации

SALT OF PYRROLIDIN-3-YL ACETIC ACID DERIVATIVE AND CRYSTALS THEREOF

Номер: US20160002165A1
Автор: Kushida Ikuo, Yoshida Kenshi
Принадлежит:

An organic carboxylic acid salt of 2-[(3S,4R)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl) piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid and a crystal thereof. 1. An organic carboxylic acid salt of 2-[(3S ,4R)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid.2. The salt according to claim 1 , which is characterized by that the organic carboxylic acid is L-mandelic acid.3. (canceled)4. A crystal of the organic carboxylic acid salt of 2-[(3S claim 1 ,4R)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid.5. The crystal according to claim 4 , which is characterized by that the organic carboxylic acid is L-mandelic acid.6. (canceled)7. The crystal according to claim 5 , which is characterized by having a diffraction peak at a diffraction angle (2θ±0.2°) of 7.2° in powder X-ray diffractometry.8. The crystal according to claim 7 , which is characterized by having further diffraction peaks at diffraction angles (2θ±0.2°) of 14.4° and 15.7° in powder X-ray diffractometry.9. The crystal according to claim 8 , which is characterized by having further diffraction peaks at diffraction angles (2θ±0.2°) of 10.3° and 23.5° in powder X-ray diffractometry.10. The crystal according to claim 9 , which is characterized by having further diffraction peaks at diffraction angles (2θ±0.2°) of 12.9° claim 9 , 14.9° claim 9 , 17.2° claim 9 , 20.10 and 24.7° in powder X-ray diffractometry.11. The crystal according to claim 5 , which is characterized by having peaks at chemical shifts (ppm) of 14.1 claim 5 , 52.9 claim 5 , 75.2 claim 5 , 144.7 and 174.0 in C solid state NMR spectrum.1215.-. (canceled) The present invention relates to a salt of a pyrrolidin-3-yl acetic acid derivative having an inhibitory action in a fractalkine-CX3CR1 pathway, and a crystal thereof ...

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Номер записи: 18
03-01-2019 дата публикации

PROCESS FOR THE PREPARATION OF CHIRAL 3-AMINO-PIPERIDINS, USEFUL INTERMEDIATES FOR THE PREPARATION OF TOFACITINIB

Номер: US20190002407A1
Автор: Miserazzi Emanuele, Pastó Aguilá Mireia, Preciado Gallego Sara
Принадлежит: F.I.S. - FABBRICA ITALIANA SINTETICI S.p.A.

Object of the present invention is an improved process for the preparation of (3R,4R)-1-benzyl-4-methylpiperidin-3-amine by means of chiral Rhodium catalysts. 2. The process according to the claim 1 , wherein the compound of formula (II) or salt thereof has an enantiomeric excess higher than 67% claim 1 , or of at least 70%.3. The process according to claim 1 , wherein the Rh(I) complex is a neutral complex of the general formula (IVa) or (IVb):{'br': None, 'sub': '2', '[RhLA]\u2003\u2003(IVa) or'}{'br': None, 'sub': '2', '[RhLA]\u2003\u2003(IVb),'}{'sub': 4-12', '2-12, 'wherein L represents a Cdiene or two Calkene molecules, and A is chlorine, bromine, iodine, trifluoromethanesulfone, tetrafluoroboarte or acetylacetonate.'}4. The process according to the claim 3 , wherein L is norbornadiene or 1 claim 3 ,5-cyclooctadiene.5. The process according to claim 3 , wherein A is trifluoromethansulfone.8. The process according to claim 1 , wherein the asymmetrical hydrogenation is carried out at a temperature from 30° C. to 60° C. and the solvent is 2 claim 1 ,2 claim 1 ,2-trifluoroethanol claim 1 , or is carried out at a temperature from 50° C. to 70° C. and the solvent is methanol.9. The process according to claim 1 , wherein the asymmetrical hydrogenation is carried out in 2 claim 1 ,2 claim 1 ,2-trifluoroethanol and the pressure is from 2 to 15 bar claim 1 , or is carried in methanol and the pressure is from 10 to 20 bar.10. The process according to claim 1 , wherein the asymmetrical hydrogenation is carried out in from 5 to 10 volumes of 2 claim 1 ,2 claim 1 ,2-trifluoroethanol or from 10 to 20 volumes of methanol.17. The process according to claim 4 , wherein A is trifluoromethansulfone. This application claims benefit to European Patent Application No. EP17178755.9, filed Jun. 29, 2017, the entire contents of which are incorporated by reference herein as if fully set forth.The object of the present invention is an improved process for the synthesis of a key ...

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Номер записи: 19
03-01-2019 дата публикации

OLIGO-GUANIDINES BASED CELLULAR TRANSPORTER COMPRISING HETEROCYCLIC RINGS WITH HYDROPHOBIC AND/OR LIPOPHILIC GROUPS AT N-TERMINAL FOR EFFECTIVE DELIVERY OF NONPENETRABLE CARGOS IN-VITRO AND IN-VIVO

Номер: US20190002408A1
Автор: BHADRA Jhuma, KUNDU Jayanta, Pattanayak Sankha, Sinha Surajit
Принадлежит:

An oligo-guanidine as cell penetrating agents/carriers includes a heterocyclic ring including 4-aminopiperidine, piperazine, morpholine having at least one N-terminal based heterocyclic ring or at least one O-heteroatom based heterocyclic ring tailored with hydrophobic and/or lipophilic group. The oligo-guanidine is adapted as an effective molecular transporter to transport and/or delivery therapeutics, therapeutic candidates, probes, or other molecules of interest across biological barriers including oligonucleotides. Advantageously, the oligo-guanidine is capable of being internalized into cells (in-vitro and in-vivo) with enhanced cellular uptake in nanomolar concentration. 1. Oligo-guanidines as cell penetrating agents and carriers comprising heterocyclic ring conjugated internally substituted oligomeric guanidines including selectively hydrophobic and/or lipophilic group with said hydrophobic and/or lipophilic group disposed in a well defined 3D structure in solution phase as a 6 member heterocyclic ring with selective positioning of the guanidinium into energetically favourable equatorial orientations enabling cellular permealization.2. Oligo-guanidines according to claim 1 , wherein said hydrophobic and/or lipophilic group is in N-terminal of a heterocyclic ring or is adjacent to O-heteroatom of the terminal heterocyclic ring.3. Oligo-guanidines according to claim 1 , with adaptibility for linkage to molecules including biomolecules to favour transport and delivery of said molecules inside a cell.4. Oligo-guanidines according to claim 2 , wherein said heterocyclic ring having hydrophobic and/or lipophilic group in its N-terminal is linked to another heterocyclic ring having covalently conjugated said molecules in its N-terminal claim 2 , through repetitive guanidinium moiety.5. Oligo-guanidines according to claim 1 , wherein said internally substituted oligomeric guanidines involve guanidinium moieties conjugated to anyone or more heterocyclic rings including ...

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Номер записи: 20
01-01-2015 дата публикации

Oximes For Treatment Of Peripheral And Central Nervous System Exposure to Acetyl Cholinesterase Inhibitors

Номер: US20150005328A1
Автор: BEMBEN Christopher J., CAMPOS Bismarck, CORBETT Richard M., MAXWELL Donald M., MCHARDY Stanton F., TIDWELL Michael W.
Принадлежит:

The present invention relates to non-charged oxime compounds which are acetyl cholinesterase (AChE) reactivators of inhibited AChE and which protect against organophosphate poisoning both peripherally and in the central nervous system. Also disclosed are pharmaceutical compositions and methods for preparing the reactivator compounds and associated intermediates. 2. The acetyl cholinesterase reactivator compound of wherein the reactivator is present as the E or Z isomer with respect to the oxime moiety.3. The acetyl cholinesterase reactivator compound of wherein said compound comprises a pharmaceutically acceptable salt comprising an acid addition salt or base addition salt.4. The acetyl cholinesterase reactivator compound of wherein said pharmaceutically acceptable salt comprises one or more of the following salts: acetate claim 3 , adipate claim 3 , aspartate claim 3 , benzoate claim 3 , besylate claim 3 , bicarbonate/carbonate claim 3 , bisulphate/sulphate claim 3 , borate claim 3 , citrate claim 3 , formate claim 3 , fumarate claim 3 , gluconate claim 3 , glucuronate claim 3 , hexafluorophosphate claim 3 , hydrochloride/chloride claim 3 , hydrobromide/bromide claim 3 , hydroiodide/iodide claim 3 , lactate claim 3 , malate claim 3 , maleate claim 3 , malonate claim 3 , mandelates claim 3 , mesylate claim 3 , methylsulphate claim 3 , naphthylate claim 3 , 2-napsylate claim 3 , nicotinate claim 3 , nitrate claim 3 , oxalate claim 3 , palmitate claim 3 , pamoate claim 3 , phosphate/hydrogen phosphate/dihydrogen phosphate claim 3 , pyroglutamate claim 3 , salicylate claim 3 , saccharate claim 3 , stearate claim 3 , succinate claim 3 , sulfonate claim 3 , stannate claim 3 , tartrate claim 3 , tosylate claim 3 , or trifluoroacetate salts.5. The acetyl cholinesterase reactivator compound of wherein said pharmaceutically acceptable salt comprises a base salt comprising one or more of the following: aluminium claim 3 , calcium claim 3 , choline claim 3 , diethylamine claim ...

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Номер записи: 21
27-01-2022 дата публикации

ANALOGS OF PRIDOPIDINE, THEIR PREPARATION AND USE

Номер: US20220023280A1
Автор: Kaljuste Kalle, Laos Marit, Maasalu Ants, Päri Malle, Schmidt Malle
Принадлежит:

This invention provides a composition comprising pridopidine or pharmaceutically acceptable salt thereof and at least one of compounds 1-8: 2. The method of claim 1 , wherein the method comprises treating claim 1 , slowing the progression claim 1 , lessening the decline claim 1 , delaying onset of symptoms or slowing the progression of symptoms of Huntington disease claim 1 , wherein the Huntington disease is an early stage Huntington disease.3. The method of claim 1 , wherein the method comprises treating claim 1 , slowing the progression claim 1 , lessening the decline claim 1 , delaying onset of symptoms or slowing the progression of symptoms of ALS.4. The method of claim 1 , wherein the method comprises treating claim 1 , slowing the progression claim 1 , lessening the decline claim 1 , delaying onset of symptoms or slowing the progression of symptoms of dystonia claim 1 , wherein the dystonia is a severe dystonia.5. The method of claim 1 , wherein the method treating claim 1 , slowing the progression claim 1 , lessening the decline claim 1 , delaying onset of symptoms or slowing the progression of symptoms of Rett Syndrome.6. The method of claim 1 , wherein the method comprises treating claim 1 , slowing the progression claim 1 , lessening the decline claim 1 , delaying onset of symptoms or slowing the progression of symptoms of a mitochondrial disease or dysfunction claim 1 , wherein the mitochondrial disease or dysfunction is Lysosomal Storage Disease (LSD) claim 1 , leukodystrophies or a vanishing white matter (VWM) disease.7. The method of claim 1 , wherein the composition comprises pridopidine or a pharmaceutically acceptable salt thereof and at least one of compound 1 claim 1 , compound 4 claim 1 , pharmaceutically acceptable salt thereof or combination thereof.8. The method of claim 1 , wherein the composition comprises pridopidine or a pharmaceutically acceptable salt thereof and compound 1 or pharmaceutically acceptable salt thereof.9. The method of ...

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Номер записи: 22
14-01-2016 дата публикации

BCL-2-SELECTIVE APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE DISEASES

Номер: US20160009687A1
Автор: Ding Hong, Elmore Steven W., Hasvold Lisa, Hexamer Laura A., Kunzer Aaron R., McClellan William J., Souers Andrew J., Sullivan Gerard M., Tao Zhi-Fu, Wendt Michael D.
Принадлежит:

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein. 114-. (canceled)15. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:2-(benzyloxy)-4-(4-((4′-chloro-1,1-′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(2-phenylethoxy)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-benzyl-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(2-phenylethyl)benzamide;2-(benzylamino)-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-methoxy-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(1H-indol-6-yloxy)benzamide;N-[(3-{[chloro(difluoro)methyl]sulfonyl}-4-{[3-(dimethylamino)propyl]amino}phenyl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-indol-4-yloxy)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H ...

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Номер записи: 23
11-01-2018 дата публикации

SYNTHESIS OF TRIACETONEDIAMINE COMPOUNDS BY REDUCTIVE AMINATION PROCEEDING FROM TRIACETONEDIAMINE AND DERIVATIVES THEREOF

Номер: US20180009734A1
Автор: MINKE KATHARINA, WILLY BENJAMIN
Принадлежит: EVONIK DEGUSSA GmbH

An N-substituted triacetonediamine compound is produced by reacting 4-amino-2,2,6,6-tetramethylpiperidine or a derivative thereof with a carbonyl compound in a reductive amination. 2. The process according to claim 1 , wherein p=p=p=p=p=p=p=p=p=p=0 and wherein p claim 1 , p claim 1 , p claim 1 , p claim 1 , p claim 1 , pare each independently 0 or 1.3. The process according to claim 1 , wherein Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yare each independently selected from the group consisting ofunbranched or branched alkylene group having 1 to 30 carbon atoms, anddivalent saturated hydrocarbyl group having 3 to 30 carbon atoms and having at least one saturated ring composed of 3 to 30 carbon atoms.5. The process according to claim 1 , wherein X=X=X=X=XXX=X=X=X=X=X claim 1 , X=X=X=hydrogen.6. The process according to claim 1 , wherein the triacetonediamine compound (I) is selected from the group consisting of the chemical structures (I-A) claim 1 , and (I-B) and wherein the R claim 1 , Rradicals are each independently selected from the group consisting ofhydrogen, and{'sub': 2', '3', '2', '3', '3', '3', '2', '2', '3', '2', '3', '2', '3', '2', '3, 'unbranched or branched alkyl group which has 1 to 12 carbon atoms and in which at least one hydrogen radical may be replaced by a radical selected from the group consisting of —OH, —NH, —OCH, —OCHCH, —NH(CH), —N(CH), —NH(CHCH), —N(CHCH), and —N(CH)(CHCH).'}7. The process according to claim 1 , wherein the triacetonediamine compound (I) is selected from the group consisting of the chemical structures (I-A) claim 1 , and (I-B) and wherein the R′ claim 1 , Rradicals are each independently selected from the group consisting ofhydrogen, andunbranched or branched alkyl group having 1 to 12 carbon atoms.8. The process according to claim 1 , wherein Z claim 1 , Z claim 1 , Zare each independently selected from the group consisting ofdirect bond, and 'divalent saturated ...

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Номер записи: 24
08-01-2015 дата публикации

Acyl Piperidine Inhibitors of Soluble Epoxide Hydrolase

Номер: US20150011586A1
Автор: Hammock Bruce D., Lee Kin Sing, Morisseau Christophe
Принадлежит:

Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases. In some embodiments, the present invention provides a method for monitoring the activity of a soluble epoxide hydrolase, the method including contacting the soluble epoxide hydrolase with an amount of a compound of the present invention sufficient to produce a detectable change in the fluorescence of the soluble epoxide hydrolase by interacting with one or more tryptophan residues present in the catalytic site of said sEH. 1. A compound selected from the group consisting of 1-(1-(2-methylbutyryl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea , (S)-1-(1-(2-methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea , 1-(1-isobutyrylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea , 1-(1-(2-ethylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea , 1-(1-(2-ethylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea , (S)-1-(1-(2-methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea , 1-cyclohexyl-3-(1-(2-methylbutanoyl)piperidin-4-yl)urea , 1-cycloheptyl-3-(1-(2-methylbutanoyl)piperidin-4-yl)urea , 1-(4-isopropylphenyl)-3-(1-(2-methyl butanoyl)piperidin-4-yl)urea , 1-(3 ,5-di-trifluoromethylphenyI)-3-(1-(2-methylbutanoyl)piperidin-4-yl)urea , 1-(4-tert-butylphenyl)-3-(1-(2-methyl butanoyl)piperidin-4-yl)urea , 1-(4-ethylcyclohexyl)-3-(1 -isobutyrylpiperidin-4-yl)urea , or salts and isomers thereof.2. The compound of claim 1 , selected from the group consisting of 1-(1-(2-methylbutyryl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea claim 1 , (S)-1-(1-(2-methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea claim 1 , 1-(1-isobutyrylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea claim 1 , and (S)-1-(1-(2-methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea claim 1 ,3. The compound of claim 1 , selected from the group consisting of (S)-1-(1-(2-methylbutanoyl) ...

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Номер записи: 25
03-02-2022 дата публикации

PROCESS FOR THE PREPARATION OF PHARMACEUTICAL AGENT

Номер: US20220033356A1
Автор: HALUSZCZUK Adam, KOSIK Kamil, PIOTRKOWSKA Barbara
Принадлежит: ZAKLADY FARMACEUTYCZNE POLPHARMA S.A.

This invention relates to a process for the preparation of pimavanserin comprising: (i) providing an acid addition salt of pimavanserin; (ii) dissolving the acid addition salt of pimavanserin in an aqueous solvent to form an aqueous solution; (iii) washing the aqueous solution obtained in step (ii) with an organic solvent; and (iv) adding a base to the washed aqueous solution to form pimavanserin. The invention also relates to a process for the preparation of an acid addition salt of pimavanserin additionally comprising step (v) of converting pimavanserin into an acid addition salt of pimavanserin. The invention also relates to pimavanserin or an acid addition salt thereof obtainable by the process, and to the use of pimavanserin hydrochloride, pimavanserin hydrogen sulfate or pimavanserin acetate for preparing pimavanserin or an acid addition salt thereof. 1. A process for the preparation of pimavanserin comprising:(i) providing an acid addition salt of pimavanserin;(ii) dissolving the acid addition salt of pimavanserin in an aqueous solvent to form an aqueous solution;(iii) washing the aqueous solution obtained in step (ii) with an organic solvent; and(iv) adding a base to the washed aqueous solution to form pimavanserin.2. A process for the preparation of an acid addition salt of pimavanserin comprising:(i) providing an acid addition salt of pimavanserin;(ii) dissolving the acid addition salt of pimavanserin in an aqueous solvent to form an aqueous solution;(iii) washing the aqueous solution obtained in step (ii) with an organic solvent;(iv) adding a base to the washed aqueous solution to form pimavanserin; and(v) converting pimavanserin into an acid addition salt of pimavanserin.3. A process as claimed in claim 2 , wherein in step (v) pimavanserin is converted into pimavanserin hemitartrate.4. A process as claimed in claim 3 , wherein prior to converting pimavanserin into pimavanserin hemitartrate in step (v) claim 3 , the process further comprises the step of ...

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Номер записи: 26
17-01-2019 дата публикации

COMPOUNDS FOR INHIBITING CANCER AND VIRUS

Номер: US20190016743A1
Автор: LIOU Jing-Ping, LIU Yun-Ru, Yen Yun
Принадлежит: TAIPEI MEDICAL UNIVERSITY

The invention relates to compounds for inhibiting a cancer cell or a virus. Particularly, the invention provides compounds for inhibiting, treating and/or preventing cancer and Zika virus. 2. The compound of claim 1 , wherein X is O; m is 1; and/or n is 2; or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein Ris halogen or Calkyl; or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.4. The compound of claim 1 , wherein Ris Cl claim 1 , or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.5. (canceled)6. The compound of claim 1 , wherein Ris glucopyranosyl claim 1 , 1 claim 1 ,4′-bipiperidinylCOC(O)CH claim 1 , or C(O)pyridinyl; or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.7. The compound of claim 1 , wherein Ris CF claim 1 , F claim 1 , Cl claim 1 , Br or NO; or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.8. The compound of claim 1 , wherein Ris CF claim 1 , Cl or NO; or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.10. A pharmaceutical composition comprising a compound of Formula (I) of or a tautomer claim 1 , stereoisomer or enantiomer thereof claim 1 , or a solvate or a pharmaceutically acceptable salt thereof.11. A method for inhibiting tumor growth in a subject claim 1 , comprising administering to the subject a therapeutically effective amount of the compound of Formula (I) of .12. A method for treating or preventing a disease associated with cell proliferation claim 1 , cell migration claim 1 , comprising administering to a subject an effective amount of the ...

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Номер записи: 27
21-01-2021 дата публикации

HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS

Номер: US20210017164A1
Автор: Lu Liang, Qian Ding-quan, Wu Liangxing, Yao Wenqing
Принадлежит:

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections. 340.-. (canceled)41. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof claim 1 , and a pharmaceutically acceptable carrier or excipient.42. A method of inhibiting PD-1/PD-L1 interaction claim 1 , said method comprising administering to an individual a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.43. A method of treating a disease or disorder associated with inhibition of PD-1/PD-L1 interaction claim 1 , said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.44. The method of claim 43 , wherein the disease or disorder is a viral infection or cancer.45. A method of enhancing claim 1 , stimulating and/or increasing the immune response in a patient claim 1 , said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof. The present application is concerned with pharmaceutically active compounds. The disclosure provides compounds as well as their compositions and methods of use. The compounds modulate PD-1/PD-L1 protein/protein interaction and are useful in the treatment of various diseases including infectious diseases and cancer.The immune system plays an important role in controlling and eradicating diseases such as cancer. However, cancer cells often develop strategies to evade or to suppress the immune system in order to favor their growth. One such mechanism is altering the expression of co-stimulatory and co-inhibitory ...

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Номер записи: 28
28-01-2016 дата публикации

Small Molecule Inhibitors of Ebola and Lassa Fever Viruses and Methods of Use

Номер: US20160024066A1
Автор: Chandran Kartik, Cunningham James, Lee Kyungae, Ren Tao
Принадлежит:

The present invention relates to compositions and methods for the treatment of infection by enveloped viruses, such as Ebola and Lassa fever viruses. 5. The method of claim 3 , wherein the viral infection is an Ebola infection.6. The method of claim 3 , wherein the viral infection is a Lassa fever infection. This application is a divisional application of U.S. patent application Ser. No. 13/818,790, which is the National Stage application of PCT/US11/050164, filed Sep. 1, 2011, which claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/379,138, filed Sep. 1, 2010, the contents of all of which are hereby incorporated by reference.This invention was made with government support under AI057159 awarded by the National Institutes of Health. The government has certain rights in the invention.Ebolaviruses (EboV) are enveloped negative-sense RNA viruses that cause sporadic outbreaks of rapidly fatal zoonotic infection. EboV is transmitted by close contact and virus levels increase by 75-fold/day for several days after initial infection. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines, including interferon-α and TNF-α in response to infection. The endothelial cell dysfunction associated with “cytokine storm” results in capillary leak, hypovolemic shock, disseminated intravascular coagulation and inadequate perfusion of major organs. In many outbreaks, the mortality rate from EboV infection exceeds 75% in 14 days. Current therapy is supportive; there is no effective anti-EboV vaccine or therapy. The unpredictable onset, ease of transmission, rapidity of progression, high mortality, and bio-terrorism potential have created a high level of public concern about EboV. Therefore, development of anti-EboV drugs is a high priority.Recent studies have identified promising drug targets. Previously, it was found that stepwise proteolytic cleavage of EboV envelope glycoprotein GP by the lysosomal cysteine ...

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Номер записи: 29
26-01-2017 дата публикации

ARYL AND HETEROARYL ETHER COMPOUNDS AS ROR GAMMA MODULATORS

Номер: US20170022195A1
Автор: ADIK Bharat G., Bajpai Malini, CHAUDHARI Sachin S., DHONE Sachin V., KADAM Ashok B., KHAIRATKAR-JOSHI Neelima, Shah Daisy M., Thomas Abraham
Принадлежит:

The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R, R, R, n, and p are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer. 157-. (canceled)59. The compound according to claim 58 , wherein R is —CH.60. The compound according to claim 58 , wherein ‘p’ is 0.63. The compound according to claim 58 , wherein Ris —F claim 58 , —Cl claim 58 , —CH claim 58 , —CHCH claim 58 , —CH(CH) claim 58 , —CF claim 58 , —OCF claim 58 , —OCF claim 58 , —CN or 4-chlorophenyl; and ‘n’ is 1 claim 58 , 2 or 3.71. The compound according to claim 70 , wherein Ris —F claim 70 , —Cl claim 70 , —CH claim 70 , —CHCH claim 70 , —CH(CH) claim 70 , —CF claim 70 , —OCF claim 70 , —OCF claim 70 , —CN or 4-chlorophenyl; and ‘n’ is 1 claim 70 , 2 or 3.74. The compound according to claim 73 , wherein{'sup': '1', 'Xis N, CH or CF;'}Ring B is phenyl;{'sup': '2', 'sub': 3', '2', '3, 'Ris —F, —Cl, —CF, —OCF, —OCFor —CN;'}‘n’ is 1, 2 or 3; and{'sup': c', 'd, 'Rand Rare independently selected from hydrogen and methyl.'}76. The compound according to claim 58 , selected from2-[4-(Ethylsulfonyl)phenyl]-N-(1-methyl-2-{2-[4-(trifluoromethyl) phenoxy]propan-2-yl}-1H-benzimidazol-5-yl)acetamide;N-{2-[2-(3,4-Difluorophenoxy)propan-2-yl]-1-methyl-1H-benzimidazol-5-yl}-2-[4-(ethylsulfonyl)phenyl]acetamide;N-{2-[1-(4-Chloro-2-fluoro-phenoxy)-1-methyl-ethyl]-1-methyl-1H-benzoimidazol-5-yl}-2-(4-ethanesulfonyl-phenyl)-acetamide;N-{2-[2-(2,4-Dichlorophenoxy)propan-2-yl]-1-methyl-1H-benzimidazol-5-yl}-2-[4-(ethylsulfonyl)phenyl]acetamide;N-{2-[2-(3,4-Dichlorophenoxy)propan-2-yl ...

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Номер записи: 30
25-01-2018 дата публикации

PIPERIDINE DERIVATIVES AS HDAC1/2 INHIBITORS

Номер: US20180022702A1
Автор: Mazitschek Ralph, van Duzer John H.
Принадлежит:

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity. 3. The compound of claim 1 , wherein Xand Xare each N.5. The compound of claim 1 , wherein Z is selected from the group consisting of C(O)NRR claim 1 , C(O)OR claim 1 , C(O)—C-C-cycloalkyl claim 1 , C(O)—C-C-heterocyclyl claim 1 , and C(O)C-alkyl-heteroaryl claim 1 , wherein heteroaryl claim 1 , cycloalkyl claim 1 , or heterocyclyl are optionally substituted by 1 or 2 of C-C-alkyl claim 1 , halo claim 1 , or hydroxy; and{'sup': '6', 'sub': '6', 'Ris C-aryl.'}6. The compound of claim 1 , wherein Z is selected from the group consisting of H claim 1 , C-C-alkyl claim 1 , and C-aryl.7. The compound of claim 1 , wherein Ris H.8. The compound of claim 1 , wherein Ris H.9. The compound of claim 1 , wherein Ris H claim 1 , methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , or phenyl.11. The compound of claim 10 , wherein Xand Xare each N.12. The compound of claim 10 , wherein Ris H.13. The compound of claim 10 , wherein Ris H claim 10 , methyl claim 10 , or isopropyl.14. The compound of claim 10 , wherein Ris H and Ris C-C-alkyl.15. The compound of claim 10 , wherein Rand Rtogether form a heterocyclyl selected from the group consisting of morpholinyl claim 10 , piperidinyl claim 10 , piperazinyl claim 10 , and pyrrolidinyl claim 10 , wherein the morpholinyl claim 10 , piperidinyl claim 10 , piperazinyl claim 10 , and pyrrolidinyl are optionally substituted by 1 or 2 of C-C-alkyl claim 10 , halo claim 10 , or hydroxy.16. The compound of claim 10 , wherein Xand Xare N;{'sup': '1', 'Ris H;'}{'sup': '2', 'Ris H;'}{'sup': '3', 'sub': 1', '4, 'Ris H or C-C-alkyl; and'}{'sup': 4', '5, 'sub': 1', '6, 'Rand Rtogether form a heterocyclyl selected from the group consisting of morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl, wherein the morpholinyl, piperidinyl, piperazinyl, and ...

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Номер записи: 31
28-01-2021 дата публикации

BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS

Номер: US20210022978A1
Автор: Erker Thomas, Schreppel Philipp
Принадлежит:

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na—K2Cl-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis. 3. The compound for use according to claim 2 , wherein Ris —COO—(Calkyl) claim 2 , wherein the alkyl moiety of said —COO—(Calkyl) is optionally substituted with one or more groups independently selected from halogen claim 2 , —CF claim 2 , —CN claim 2 , —NO claim 2 , —NH claim 2 , —NH(Calkyl) claim 2 , —N(Calkyl)(Calkyl) claim 2 , —OH claim 2 , —O(Calkyl) claim 2 , —SH and —S(Calkyl) claim 2 , and further wherein one or two —CH— units comprised in the alkyl moiety of said —COO—(Calkyl) are each optionally replaced by a group independently selected from —O— claim 2 , —CO— claim 2 , —COO— claim 2 , —O—CO— claim 2 , —NH— claim 2 , —N(Calkyl)- claim 2 , —NH—CO— claim 2 , —N(Calkyl)-CO— claim 2 , —CO—NH— claim 2 , —CO—N(Calkyl)- claim 2 , —S— claim 2 , —SO— claim 2 , —SO— claim 2 , —SO—NH— claim 2 , —SO—N(Calkyl)- claim 2 , —NH—SO— and —N(Calkyl)-SO—.4. The compound for use according to or claim 2 , wherein Ris —COO—CH.5. The compound for use according to claim 2 , wherein Ris —COOH.6. The compound for use according to claim 2 , wherein Ris selected from —(Calkylene)-NH—(Calkylene)-R claim 2 , —COO—(Calkylene)-R claim 2 , —O—CO—(Calkylene)-R claim 2 , —CO—(Calkylene)-R claim 2 , —CO—NH—(Calkylene)-R claim 2 , —CO—N(Calkyl)-(Calkylene)-R claim 2 , —NH—CO—(Calkylene)-Rand —N(Calkyl)-CO—(Calkylene)-R claim 2 , wherein Ris independently selected from —CF claim 2 , —CN and halogen.7. The compound for use according to or claim 2 , wherein Ris —(Calkylene)-NH—(Calkylene)-CF.8. The compound for use according to any one of to claim 2 , wherein Ris hydrogen.9. The compound for use according to any one of to claim 2 , wherein Ris selected from —SO—NH claim 2 , —SO—NH(Calkyl ...

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Номер записи: 32
28-01-2021 дата публикации

ATYPICAL INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF

Номер: US20210024523A1
Автор: GIANCOLA JoLynn Barbara, Newman Amy Hauck, Slack Rachel D.
Принадлежит:

Disclosed herein are a series of modafinil analogue compounds that bind with moderate to high affinity to the dopamine (DA) transporter (DAT) and several analogues also having affinity for the serotonin (5-HT) transporter (SERT) and/or sigma-1 receptor. Employing aminopiperidine, piperidineamino, spirobicyclodiaza, or substituted piperazine functional groups, desired dopamine transporter affinity has been retained along with improved metabolic stability over unsubstituted piperazine ring analogues. Importantly, these compounds have no predicted addictive liability. Also disclosed are methods for treating substance use disorders as well as other neuropsychiatric disorders such as ADHD, depression, narcolepsy, and cognitive impairment. 2. A compound or salt of in which each of Rand Rindependently is an optionally substituted phenyl.3. A compound or salt of in which Y is S or S(O).4. A compound or salt of wherein the substitution on Rand Ris fluoro.5. A compound or salt of in which Z is O or 2H.6. A compound or salt of wherein n is 2 and m is 0.7. A compound or salt of wherein Ris C-Calkyl claim 1 , C-Chaloalkyl claim 1 , aryl-(C═O)— claim 1 , monocyclic heteroaryl-(C═O)— claim 1 , bicyclic heteroaryl-(C═O)— claim 1 , (C-Ccycloalkyl)C-Calkyl claim 1 , (heterocycloalkyl)C-Calkyl claim 1 , (heterocycloalkenyl)C-Calkyl claim 1 , (aryl)C-Calkyl claim 1 , (monocyclic heteroaryl)C-Calkyl claim 1 , (bicyclic heteroaryl)C-Calkyl claim 1 , or (C-Calkanoyl)C-Calkyl claim 1 , wherein each alkyl independently can optionally be substituted with 1 or 2 substituents claim 1 , specifically substituted with 1 hydroxyl claim 1 , and each aryl and heteroaryl independently can optionally be substituted with 1 claim 1 , 2 claim 1 , or 3 substituents.12. A compound or salt of wherein a sulfoxide fragment has an (R)-configuration or an (S)-configuration.17. A compound or salt of as disclosed in Table 1 or Table 2.18. A compound of claim 1 , comprising 1-((2S claim 1 ,6R)-4-(2-(bis(4- ...

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Номер записи: 33
04-02-2016 дата публикации

NEW ARYLAMINOALCOHOL DERIVATIVES WITH ANTIPLASMODIAL ACTIVITY

Номер: US20160031815A1
Автор: ALDANA MORAZA Ignacio, BLAIR TRUJILLO Silvia Victoria, DEHARO Eric, GARAVITO Giovanny, MENDOZA LIZALDEZ Adela, PEREZ-SILANES Silvia
Принадлежит: INSTITUT DE RECHERCHE POUR LE DEVELOPPEMENT

The present invention relates to new arylaminoalcohol derivatives of formula (I), and to a method for the preparation of such compounds: I The invention also relates to the use of these compounds as medicaments, and in particular for the prevention and/or the treatment of parasitic diseases caused by apicomplexan parasites such as malaria and toxoplasmosis. Finally, the invention relates to pharmaceutical compositions containing such compounds of formula (I) as active principles. 2. Compound according to claim 1 , wherein the aromatic group Ar is substituted by an halogen atom claim 1 , and preferably by a fluorine atom.3. Compound according to claim 2 , wherein the aromatic group Ar is selected from the 4-fluoro-1-phenyl and 4-fluoro-1-naphtyl groups claim 2 , and preferably Ar is the 4-fluoro-1-phenyl group.4. Compound according to claim 1 , wherein the amino entity Am is a tetrahydropyridine entity.5. Compound according to claim 1 , wherein R is —NOor —F.6. Compound according to claim 1 , wherein R′ is —H or —CF.7. Compound according to claim 5 , wherein R═—NOand R′═—CF.9. Compound of formula (I) according to claim 1 , or one of its tautomeric claim 1 , racemic claim 1 , enantiomeric or polymorphic forms or pharmaceutically acceptable salts claim 1 , for its use as a medicament.10. Compound of formula (I) for its use according to claim 9 , for the prevention and/or the treatment of parasitic diseases involving apicomplexan parasites.11Plasmodium, Babesia, Toxoplasma, Neospora, Cryptosporidium, Theileria, SarcosystisEimeria.. Compound of formula (I) for its use according to claim 10 , wherein said apicomplexan parasites are selected from and12. Compound of formula (I) for its use according to for the prevention and/or the treatment of malaria.13. Compound of formula (I) for its use according to to for the prevention and/or the treatment of toxoplasmosis.14. Compound of formula (I) for its use according to for the prevention and/or the treatment of AIDS virus.15. A ...

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Номер записи: 34
31-01-2019 дата публикации

PHENYL DERIVATIVE

Номер: US20190030010A1
Автор: KAKUUCHI Akito, KUSUMI Kensuke, NAGANAWA Atsushi, NONAKA Shigeyuki, Otsuki Kazuhiro, SEKIGUCHI Tetsuya, SHINOZAKI Koji, Yamamoto Hiroshi
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

The compound of the formula (I-1): 2. The method according to claim 1 , wherein the ring 1 and the ring 2 each independently are (1) a benzene claim 1 , (2) cyclohexane or (3) pyridine ring.3. The method according to claim 1 , wherein the compound of formula (I-A) is 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid or a salt thereof.4. The method according to claim 1 , wherein the protecting group T comprises a carbonyl group.5. The method according to claim 4 , wherein the protecting group T is a 2 claim 4 ,2 claim 4 ,2-trichloroethoxycarbonyl (Troc) group claim 4 , a phenoxycarbonyl group claim 4 , or a p-nitrophenoxycarbonyl group.6. The method according to claim 2 , wherein the compound of formula (I-A) is 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid or a salt thereof.7. The method according to claim 1 , wherein the ring 1 and the ring 2 each independently are a benzene.8. The method according to claim 2 , wherein the ring 1 and the ring 2 each independently are a benzene.9. The method according to claim 1 , wherein the base is selected from the group consisting of pyridine claim 1 , triethylamine claim 1 , dimethylaniline claim 1 , dimethylaminopyridine claim 1 , diisopropylethylamine claim 1 , or a mixture thereof.10. The method according to claim 1 , wherein the organic solvent is selected from N claim 1 ,N-dimethylacetamide claim 1 , chloroform claim 1 , dichloromethane claim 1 , diethyl ether claim 1 , tetrahydrofuran claim 1 , and a mixture thereof.11. The method according to claim 2 , wherein the base is selected from the group consisting of pyridine claim 2 , triethylamine claim 2 , dimethylaniline claim 2 , dimethylaminopyridine claim 2 , diisopropylethylamine claim 2 , or a mixture thereof.12. The method according to claim 2 , wherein the organic solvent is selected from N claim 2 ,N-dimethylacetamide claim 2 ...

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Номер записи: 35
31-01-2019 дата публикации

SELECTIVE SEROTONIN 2A/2C RECEPTOR INVERSE AGONISTS AS THERAPEUTICS FOR NEURODEGENERATIVE DISEASES

Номер: US20190030015A1
Автор: ANDERSSON Carl-Magnus A., BRANN Mark R., DAVIS Robert E., Uldam Allan K., WEINER David M.
Принадлежит:

Behavioral pharmacological data with the compound of formula (I), a novel and selective 5HT2A/2C receptor inverse agonist, demonstrate in vivo efficacy in models of psychosis and dyskinesias. This includes activity in reversing MK-801 induced locomotor behaviors, suggesting that this compound may be an efficacious anti-psychotic, and activity in an MPTP primate model of dyskinesias, suggesting efficacy as an anti-dyskinesia agent. These data support the hypothesis that 5HT2A/2C receptor inverse agonism may confer antipsychotic and anti-dyskinetic efficacy in humans, and indicate a use of the compound of formula (I) and related agents as novel therapeutics for Parkinson's Disease, related human neurodegenerative diseases, and psychosis. 186-. (canceled)88. The method of claim 87 , wherein the disease or disorder is migraine.89. The method of claim 87 , wherein the disease or disorder is vasospasm.90. The method of claim 87 , wherein the disease or disorder is hypertension.91. The method of claim 87 , wherein the disease or disorder is a thrombotic condition is myocardial infarction claim 87 , stroke claim 87 , or thrombocytopenic purpura.92. The method of claim 91 , wherein the stroke is thrombotic or ischemic stroke.93. The method of claim 91 , wherein the thrombocytopenic purpura is idiopathic or thrombotic thrombocytopenic purpura.94. The method of claim 87 , wherein the disease or disorder is a peripheral vascular disease.95. The method of claim 87 , wherein a tartrate salt of the compound of Formula (I) is administered to the patient.96. The method of claim 95 , wherein the tartrate salt of the compound of Formula (I) in an amount of about 0.001 mg to about 50 mg is administered to the patient.97. The method of claim 95 , wherein the tartrate salt of the compound of Formula (I) in an amount of about 15 mg is administered to the patient.98. The method of claim 95 , wherein the tartrate salt of the compound of Formula (I) in an amount of about 25 mg is ...

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Номер записи: 36
31-01-2019 дата публикации

ANALOGS OF PRIDOPIDINE, THEIR PREPARATION AND USE

Номер: US20190030016A1
Автор: Kaljuste Kalle, Laos Marit, Maasalu Ants, Päri Malle, Schmidt Malle
Принадлежит: TEVA PHARMACEUTICAL INDUSTRIES LTD.

This invention provides an isolated compound having the structure: 17. A pharmaceutical composition comprising an amount of pridopidine and at least one of Compound 1 , Compound 2 , Compound 3 , Compound 4 , Compound 5 , Compound 6 , and Compound 7 whereina) Compound 1 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, orb) Compound 2 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, orc) Compound 3 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, ord) Compound 4 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, ore) Compound 5 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, orf) Compound 6 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, org) Compound 7 is present in the pharmaceutical composition in an amount not more than 10 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method.18. The pharmaceutical composition of claim 17 , whereina) Compound 1 is present in the pharmaceutical composition in an amount not more than 0.15 area-% relative to the concentration of pridopidine, based on a determination by an HPLC method, orb) Compound 2 is present in the pharmaceutical composition in an amount not more than 0.15 area-% relative to the concentration of pridopidine, based on a determination by an HPLC ...

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Номер записи: 37
30-01-2020 дата публикации

ANALOGS OF PRIDOPIDINE, THEIR PREPARATION AND USE

Номер: US20200030308A1
Автор: Kaljuste Kalle, Laos Marit, Maasalu Ants, Päri Malle, Schmidt Malle
Принадлежит:

This invention provides an isolated compound having the structure: 2. The composition of claim 1 , wherein the composition comprises pridopidine and at least one of compound 1 claim 1 , compound 4 or combination thereof.3. The composition of claim 1 , wherein the composition comprises pridopidine salt claim 1 , wherein the salt is hydrochloride claim 1 , hydrobromide claim 1 , nitrate claim 1 , perchlorate claim 1 , phosphate claim 1 , sulphate claim 1 , formate claim 1 , acetate claim 1 , aconate claim 1 , ascorbate claim 1 , benzenesulphonate claim 1 , benzoate claim 1 , cinnamate claim 1 , citrate claim 1 , embonate claim 1 , enantate claim 1 , fumarate claim 1 , glutamate claim 1 , glycolate claim 1 , lactate claim 1 , maleate claim 1 , malonate claim 1 , mandelate claim 1 , methane-sulphonate claim 1 , naphthalene-2-sulphonate claim 1 , phthalate claim 1 , salicylate claim 1 , sorbate claim 1 , stearate claim 1 , succinate claim 1 , tartrate or toluene-p-sulphonate salt.4. The composition of claim 1 , in the form of a capsule claim 1 , a tablet claim 1 , a pill claim 1 , a powder claim 1 , a granule claim 1 , a liquid solution or a liquid suspension.5. The composition of claim 1 , in an oral dosage unit form.6. The composition of claim 5 , wherein the oral dosage unit form comprises between 22.5-315 mg pridopidine.7. The composition of claim 6 , wherein the oral dosage unit form comprises between 45-250 mg pridopidine.8. The composition of claim 7 , wherein the oral dosage unit form comprises between 45-135 mg pridopidine.9. The composition of claim 8 , wherein the oral dosage unit form comprises between 90-315 mg pridopidine.10. The composition of claim 6 , wherein the oral dosage unit form comprises about 22.5 mg pridopidine claim 6 , about 45 mg pridopidine claim 6 , about 67.5 mg pridopidine claim 6 , about 90 mg pridopidine claim 6 , about 100 mg pridopidine claim 6 , about 112.5 mg pridopidine claim 6 , about 125 mg pridopidine claim 6 , about 135 mg ...

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Номер записи: 38
04-02-2021 дата публикации

CYCLOPROPYLAMINES AS LSD1 INHIBITORS

Номер: US20210032244A1
Автор: Courter Joel R., He Chunhong, Qian Ding-quan, SHEN BO, Wang Xiaozhao, Wu Liangxing, Yao Wenqing, Zhang Fenglei
Принадлежит:

The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer. 29.-. (canceled)10. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is 0.11. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is 1.12. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is 2.13. (canceled)14. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from F and methoxy.1519.-. (canceled)20. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —CH—.2124.-. (canceled)25. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring C is cyclopentyl.26. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring C is cyclobutyl.27. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring C is cyclopropyl.2847.-. (canceled)48. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris cyanomethyl.49. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris methoxymethyl.5052.-. (canceled)53. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , having a trans configuration with respect to the di-substituted cyclopropyl group depicted in Formula I.5467.-. (canceled)68. The method of claim 1 , wherein the compound is 1-{[4-(methoxymethyl)-4-({[(1R claim 1 ,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid claim 1 , or a pharmaceutically acceptable salt thereof.69. The method of claim 1 , wherein the compound is 1-{[4-(methoxymethyl)-4-({[(1R claim 1 ,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid claim 1 , or a pharmaceutically ...

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Номер записи: 39
01-02-2018 дата публикации

Organic light-emitting device

Номер: US20180033987A1
Автор: Jang-Joo Kim, Jin-Won Sun
Принадлежит: SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

An organic light-emitting device is provided, including: a first electrode; a second electrode; and an organic layer between the first electrode and the second electrode, wherein the organic layer includes an emission layer; the emission layer includes a first compound, a second compound, a third compound, and a fourth compound; and a lowest excited triplet energy level (H T1 ) of the first compound, a lowest excited triplet energy level (DFD T1 ) of the third compound, and a lowest excited triplet energy level (FD T1 ) of the fourth compound satisfy Inequation 1: H T1 >DFD T1 >FD T1 .  <Inequation 1>

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Номер записи: 40
11-02-2016 дата публикации

PHENYL DERIVATIVE

Номер: US20160039757A1
Автор: KUSUMI Kensuke, NAGANAWA Atsushi, Otsuki Kazuhiro, SEKIGUCHI Tetsuya, SHINOZAKI Koji, Yamamoto Hiroshi, YAMAMOTO Yasuko
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

An object of the present invention is to provide a compound having strong human S1Pantagonistic activity in order to develop a useful medicament for therapy of a S1P-mediated disease such as a disease resulting from vascular constriction, fibrosis and respiratory disease. The compound represented by the general formula (I), wherein all the symbols have the same meanings as described in the specification, has a halogen atom or a haloalkyl group and a phenoxy group at certain substitution sites, and thus has strong human S1Pantagonistic activity. Therefore, the compound can be a therapeutic agent for a S1P-mediated disease, such as a disease resulting from vascular constriction, fibrosis and respiratory disease. 2. The compound according to claim 1 , wherein Ris (1) a C1-8 alkyl group which may be substituted with 1 to 5 Rgroups claim 1 , or (2) a C3-7 carbocycle which may be substituted with 1 to 5 substituents selected from the group consisting of a C1-4 alkyl group claim 1 , a C1-4 haloalkyl group claim 1 , a C1-4 alkoxy group and a halogen atom.3. The compound according to or claim 1 , wherein Mis (1) —O— or (2) —C(O)O—.5. The compound according to claim 4 , wherein Ris a hydrogen atom.6. The compound according to or claim 4 , wherein the ring 1 is (1) a benzene claim 4 , (2) cyclohexane or (3) pyridine ring.7. The compound according to claim 4 , which is 2-{3-[3-{[(3-cyclohexyl-3-hydroxy-1-pyrrolidinyl)carbonyl]amino}-5-(trifluoromethyl)phenoxy]phenyl}-2-methylpropanoic acid claim 4 , 4-cyclopentyl-4-hydroxy-N-[3-{4-[(methylsulphonyl)carbamoyl]phenoxy}-5-(trifluoromethyl)phenyl]-1-piperidine carboxamide claim 4 , 4-cyclopentyl-N-[3-{4-[(ethylsulphonyl)carbamoyl]phenoxy}-5-(trifluoromethyl)phenyl]-4-hydroxy-1-piperidine carboxamide claim 4 , 1-{4-[3-{[(3-cyclohexyl-3-hydroxy-1-pyrrolidinyl)carbonyl]amino}-5-(trifluoromethyl)phenoxy]phenyl}cyclopropanecarboxylic acid claim 4 , 2-{4-[3-{[(3-cyclohexyl-3-hydroxy-1-pyrrolidinyl)carbonyl]amino}-5-(trifluoromethyl) ...

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Номер записи: 41
09-02-2017 дата публикации

SUBSTITUTED N-(2-(AMINO)-2OXOETHYL)BENZAMIDE INHIBITORS OF AUTOTAXIN AND THEIR PREPARATION AND USE IN THE TREATMENT OF LPA-DEPENDENT OR LPA-MEDIATED DISEASES

Номер: US20170037007A1
Автор: Babiss Lee, Mulvihill Mark J., Ni Haihong, Renzetti Louis, Ruebsam Frank, Wang Ce, ZHANG YING
Принадлежит:

The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX. 2. The compound or salt of any one of the preceding claims , wherein:{'sup': '1', 'sub': 0-8', '3-8', '0-8', '0-8, 'Ris selected from Calkyl-, Ccycloalkyl-Calkyl-, or aryl-Calkyl-;'}{'sup': 1', '12, 'sub': 3', '3', '3', '3', '2', '2', '0-8', '2-8', '2-8', '3-8', '0-8', '3-8', '0-8', '0-8', '0-8', '0-8', 'n1, 'Gis selected from one or more of D, halo, —CN, —CD, —OCD, -oxo-, —CF, —OCF, —OCHF, —B(OH), —Calkyl, —Calkenyl, —Calkynyl, Ccycloalkyl-Calkyl-, Cheterocycloalkyl-Calkyl-, aryl-Calkyl-, heteroaryl-Calkyl-, —OCalkyl, or —S(O)R.'}3. The compound or salt of any one of the preceding claims , wherein Gis selected from 0 to 3 of D , halo , —CN , —CD , —OCD , -oxo- , —CF , —OCF , —OCHF , —B(OH) , —Calkyl , —Calkenyl , —Calkynyl , Ccycloalkyl-Calkyl- , Cheterocycloalkyl-Calkyl- , aryl-Calkyl- , heteroaryl-Calkyl- , —OCalkyl , or —S(O)R.4. The compound or salt of any one of the preceding claims , wherein:{'sup': '1', 'sub': 0-2', '4-6', '0-2', '0-2, 'Ris selected from Calkyl-, Ccycloalkyl-Calkyl-, or aryl-Calkyl-;'}{'sup': 1', '12, 'sub': 3', '3', '3', '3', '2', '2', '0-2', '2-4', '2-4', '4-6', '0-2', '4-6', '0-2', '0-3', '0-2', '0-2', 'n1, 'Gis selected from one or more of D, halo, —CN, —CD, —OCD, -oxo-, —CF, —OCF, —OCHF, —B(OH), —Calkyl, —Calkenyl, —Calkynyl, Ccycloalkyl-Calkyl-, Cheterocycloalkyl-Calkyl-, aryl-Calkyl-, heteroaryl-Calkyl-, —OCalkyl, or —S(O)R.'}5. The compound or salt of any one of the preceding claims , wherein Gis selected from is selected from 0 to 2 of D , halo , —CN , —CD , —OCD , -oxo- , —CF , —OCF , —OCHF , —B(OH) , —Calkyl , —Calkenyl , —Calkynyl , Ccycloalkyl-Calkyl- , Cheterocycloalkyl-Calkyl- ...

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Номер записи: 42
08-02-2018 дата публикации

PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF PIMAVANSERIN

Номер: US20180037549A1
Автор: Biljan Tomislav, Dogan Jasna, Metsger Leonid, Pipercic Sara Morasi, RATKAJ Marina, Skugor Maja Matanovic, WANG Yi
Принадлежит:

The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes. 121-. (canceled)25. The compound of formula (XVIII) or (XIX) of claim 22 , wherein Ris 2-methylpropan-oxy.27. The process of claim 26 , wherein Ris an isobutoxy group.34. The process of claim 33 , wherein the compound of formula (V) is prepared by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one.36. The process of claim 35 , wherein the compound of formula (V) by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one.38. The process of claim 37 , wherein the compound of formula (V) by reacting 4-fluorobenzylamine with 1-methylpiperidine-2-one. This application claims the benefit of U.S. Provisional Application Nos. 62/126,840, filed Mar. 2, 2015; 62/161,421, filed May 14, 2015; 62/187,668, filed Jul. 1, 2015; 62/188,992, filed Jul. 6, 2015; 62/198,218, filed Jul. 29, 2015; and 62/270,310, filed Dec. 21, 2015, the entireties of which are incorporated by reference herein.The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes.Pimavanserin tartrate, 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea L-hemi-tartrate, has the following chemical structure:Pimavanserin tartrate was developed by Acadia Pharmaceuticals and was approved under the trade name NUPLAZID® for use in patients with Parkinson's disease psychosis.Pimavanserin free base and its synthesis are disclosed in U.S. Pat. No. 7,601,740 (referred to herein as US '740 or the '740 patent) and U.S. Pat. No. 7,790,899 (referred to herein as US '899 or the '899 patent). US '740 discloses the synthesis of Pimavanserin free base (also referred to herein as “Compound A”), which includes O-alkylation followed by ester hydrolysis, and then in situ azidation. This ...

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Номер записи: 43
08-02-2018 дата публикации

Process for the Preparation of (3R,4R)-(1-BENZYL-4-METHYLPIPERIDIN-3-YL)-METHYLAMINE

Номер: US20180037551A1
Автор: Bonde Nilesh L., Das Arijit, Kekan Ankush Sampat, Patil Yogesh Subhash, Sathe Dhananjay G.
Принадлежит:

The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: The present application is a divisional of U.S. patent application Ser. No. 15/590,408 filed May 9, 2017, which is a divisional of U.S. patent application Ser. No. 14/891,028, filed on Nov. 13, 2015, which is U.S. National Phase filing of International Application No. PCT/IB2014/066510, filed on Dec. 2, 2014, designating the United States of America and claiming priority to Indian Patent Application No. 3843/MUM/2013, filed Dec. 9, 2013, and this application claims priority to and the benefit of the above-identified applications, which are all incorporated by reference herein in their entireties.The present invention provides an efficient and improved process for the preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine; a key starting material for the synthesis of 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxo-propanenitrile.3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxo-propanenitrile,2-hydroxypropane-1,2,3-tricarboxylate described as FORMULA I below and as disclosed in WO 02/096909, U.S. Pat. No. 7,301,023. US FDA approved it for rheumatoid arthritis.The key step for the preparation of 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxo-propanenitrile as depicted in (Scheme-1) WO 02/096909 includes:The most important part for the preparation of FORMULA I is the synthesis of (3R,4R)-(1-Benzyl-4-methylpiperidin-3-yl)-methylamine as it is very tedious synthesis and also requires very expensive reagent. There are several processes reported in literature for the synthesis and resolution of racemic (1-Benzyl-4-methylpiperidin-3-yl)-methylamine to (3R,4R)-(1-Benzyl-4-methylpiperidin-3-yl)-methylamine.WO 2007/012953 discloses preparation of 1-Benzyl-3-methoxycarbonylamino-4- ...

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Номер записи: 44
07-02-2019 дата публикации

METHOD FOR SYNTHESIZING N,N'-BIS(2,2,6,6-TETRAMETHYL-4-PIPERIDYL)-1,3-BENZENEDICARBOXAMIDE

Номер: US20190040011A1
Автор: GAI XUQIAO, ZHANG Xiuxiu
Принадлежит:

The present invention relates to a method for synthesizing N,N′-bis(2,2,6,6-tetramethyl-4-piperidyl)-1,3-benzenedicarboxamide as shown in the following formula (III), 2. The synthetic method according to claim 1 , characterized in that the solid supported catalyst is prepared by a method comprising the following steps:S1: treating a KIT-1 molecular sieve with 120° C. to 130° C. water vapor for 20 to 30 minutes, then naturally cooling to room temperature and thoroughly drying in vacuum to obtain a heat-treated molecular sieve;S2: immersing the heat-treated molecular sieve in a nitric acid aqueous solution with a molar concentration of 0.5 to 0.7 mol/L for 2 to 3 hours and then thoroughly washing with deionized water and completely drying to obtain an acid-treated molecular sieve;S3: preparing a nickel chloride aqueous solution with a molar concentration of 1.0 mol/L and a lanthanum trifluoromethanesulfonate aqueous solution with a molar concentration of 0.4 mol/L respectively;S4: impregnating the acid-treated molecular sieve with the nickel chloride aqueous solution, enabling the mass ratio of adsorbed nickel ions to the heat-treated molecular sieve of Step 1 to be (0.05 to 0.08) to 1, and then completely drying to obtain a nickel ion supported molecular sieve; andS5: impregnating the nickel ion supported molecular sieve with the lanthanum trifluoromethanesulfonate aqueous solution until the molar ratio of the adsorbed lanthanum ions to the adsorbed nickel ions in step S4 is (1.5 to 2.5) to 1, and then completely drying again to obtain the solid supported catalyst.3. The synthetic method according to claim 2 , characterized in that the mass ratio of the adsorbed nickel ions to the heat-treated molecular sieve obtained in step S1 is (0.05 to 0.08) to 1 in step S4.4. The synthetic method according to claim 2 , characterized in that the molar ratio of the adsorbed lanthanum ions to the adsorbed nickel ions in step S4 is (1.5 to 2.5) to 1 claim 2 , most preferably 2 to 1 ...

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Номер записи: 45
12-02-2015 дата публикации

COMPOUNDS AND METHODS FOR INHIBITING CIF VIRULENCE FACTOR

Номер: US20150045389A1
Автор: Bahl Christopher D., Hammock Bruce D., Madden Dean R., Morisseau Christophe
Принадлежит:

The present invention is a screening assay for identifying inhibitors of CFTR Inhibitory Factor as well as compounds identified by the screening assay for use in compositions and methods for ameliorating or treating a respiratory disease such as cystic fibrosis or secondary infection thereof. 24-. (canceled)5. A method for ameliorating or treating a respiratory disease claim 1 , or a secondary infection thereof claim 1 , comprising administering to a subject in need of treatment the pharmaceutical composition of claim 1 , thereby ameliorating or treating the subject's respiratory disease claim 1 , or secondary infection thereof.67-. (canceled)8. A method for identifying an inhibitor of Cystic fibrosis transmembrane conductance regulator Inhibitory Factor (Cif) activity comprisingcontacting a prokaryotic Cif protein with a test compound in the presence of cyano(6-methoxynaphthalen-2-yl)methyl (oxiran-2-ylmethyl) (CMNGC); anddetermining whether the test compound inhibits hydrolysis of CMNGC, thereby identifying an inhibitor of Cif activity.9. An inhibitor identified by the method of .1113-. (canceled) This invention was made with government support under contract numbers T32-AI007519, T32-DK007301, R01-AI091699, R01-DK075309 and R01-ES002710 awarded by the National Institutes of Health. The government has certain rights in the invention. Work on this invention was also supported by grants from the Cystic Fibrosis Foundation.is a Gram-negative opportunistic pathogen that commonly causes ocular and pulmonary infections, as well as burn wound infections. This bacterium possesses an inherent resistance to most antibiotics, and is able to form biofilms that further enhance antibiotic resistance and chronic infections (Davies & Bilton (2009) 54:628-40). Of particular clinical importance is the prominence of infection in patients with compromised pulmonary function. By the age of 18, 80% of all patients with cystic fibrosis (CF) have a chronic lung infection (Geller (2009) ...

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Номер записи: 46
15-02-2018 дата публикации

PHENYL DERIVATIVE

Номер: US20180042908A1
Автор: KAKUUCHI Akito, KUSUMI Kensuke, NAGANAWA Atsushi, NONAKA Shigeyuki, Otsuki Kazuhiro, SEKIGUCHI Tetsuya, SHINOZAKI Koji, Yamamoto Hiroshi
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

The compound of the formula (I-1): 1. A method of preventing and/or treating a S1P2-mediated disease , comprising administering to a mammal an effective amount of 2-{4-[3-(4-fluorophenoxy)-5-{[(4-hydroxy-4-isobutyl-1-piperidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid , or a salt thereof.2. The method according to claim 1 , wherein the S1P2-mediated disease is a disease resulting from vascular constriction claim 1 , fibrosis claim 1 , peripheral arterial occlusive disease claim 1 , hepatitis claim 1 , hepatic cirrhosis claim 1 , or hepatic failure.3. The method according to claim 2 , wherein the disease resulting from vascular constriction is cerebral vasospastic disease claim 2 , cardiac vasospastic disease claim 2 , coronary vasospastic disease claim 2 , hypertension claim 2 , pulmonary hypertension claim 2 , myocardial infarction claim 2 , angina claim 2 , arrhythmia claim 2 , portal hypertension claim 2 , varix claim 2 , or ischemia-reperfusion injury.4. The method according to claim 2 , wherein the fibrosis is pulmonary fibrosis claim 2 , hepatic fibrosis claim 2 , kidney fibrosis claim 2 , myocardial fibrosis claim 2 , or skin fibrosis. This is a Divisional of U.S. patent application Ser. No. 15/089,690 filed Apr. 4, 2016 (allowed), which is a Divisional of U.S. patent application Ser. No. 14/592,100 filed Jan. 8, 2015 (issued as U.S. Pat. No. 9,340,499 on May 17, 2016), which is a Continuation of U.S. application Ser. No. 14/347,178 filed Mar. 25, 2014 (issued as U.S. Pat. No. 8,975,409 on Mar. 10, 2015), which is a National Stage Entry of PCT International Application No. PCT/JP2012/074968 filed Sep. 27, 2012, which claims benefit of Japanese Patent Application No. 2011-213987 filed Sep. 29, 2011 of which disclosures are incorporated herein by reference in their entirety.The present invention relates to a compound represented by the formula (I-1):wherein all the symbols have the same meanings as described hereinbelow, and a salt thereof, a ...

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Номер записи: 47
01-05-2014 дата публикации

ASYMMETRIC UREAS AND MEDICAL USES THEREOF

Номер: US20140121210A1
Автор: GARCIA RUBIO Silvina, GIULIANO Claudio, Li Zhigang, PIETRA Claudio
Принадлежит: HELSINN HEALTHCARE SA

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general formula (I): 135.-. (canceled)36. A method of agonizing activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a compound selected from the group consisting of 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1 ,3 ,3-trimethylpiperidin-4-yl)urea , 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea , and 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea , or a pharmaceutically acceptable salt thereof.37. A method of treating a disease or disorder associated with expression or activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a ghrelin receptor agonist selected from the group consisting of 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1 ,3 ,3-trimethylpiperidin-4-yl)urea , 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea , and 3-(1-(2 ,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea , or a pharmaceutically acceptable salt thereof.38. The method of claim 37 , wherein said disease or disorder is an eating disorder claim 37 , gastrointestinal disease claim 37 , gastric disorder claim 37 , or cachexia resulting from cancer claim 37 , congestive heart failure claim 37 , wasting due to ageing or AIDS.39. The method of claim 38 , wherein said eating disorder is anorexia nervosa.40. The method of claim 38 , wherein said gastric disorder is selected from the group consisting of Post-operative ileus (POI) claim 38 , diabetic gastroparesis claim 38 , and opioid induced bowel dysfunction.41. The method of claim 38 , wherein said gastrointestinal disease is selected from the group consisting of irritable bowel syndrome claim 38 , ...

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Номер записи: 48
06-02-2020 дата публикации

NANOPLASMONIC PAPER SUBSTRATE FOR IDENTIFICATION OF FENTANYL AND FENTANYL-RELATED COMPOUNDS

Номер: US20200041418A1
Автор: Weatherston Joshua D., Wu Hung-Jen
Принадлежит:

In an embodiment, a method to detect analytes, the method including contacting a sample on a substrate, where the substrate is a nanoplasmonic paper, performing surface-enhanced Raman scattering detection with paper chromatography separation on the substrate, and identifying at least one analyte in the sample. In a further embodiment, an apparatus to detect analytes, the apparatus including a vacuum pump coupled to a filtration unit operable to collect solid particles off an object and the filtration unit including a filter substrate, where the filter substrate includes nanoplasmonic paper. 1. A method to detect analytes , the method comprising:contacting a sample on a substrate, wherein the substrate is a nanoplasmonic paper;performing surface-enhanced Raman scattering detection with paper chromatography separation on the substrate; andidentifying at least one analyte in the sample.2. The method of claim 1 , wherein the nanoplasmonic paper comprises glass microfiber filter paper coated with silver nanoparticles.3. The method of claim 2 , wherein the silver nanoparticles are coated on the nanoplasmonic paper via a silver mirror reaction.4. The method of claim 1 , wherein the substrate comprises a compound to enhance affinity between the substrate and the at least one analyte to thereby increase detection limit.5. The method of claim 4 , wherein the compound is selected from the group consisting of organic compounds claim 4 , inorganic compounds claim 4 , thiols claim 4 , functional groups claim 4 , functional molecules claim 4 , 1-butanethiol claim 4 , or combinations thereof.6. The method of claim 1 , wherein the sample is a mixed-analyte sample comprising a plurality of analytes.7. The method of claim 1 , wherein the contacting comprises collecting solid particles of the sample onto the substrate via vacuum.8. The method of claim 7 , wherein the nanoplasmonic paper is extended between a first end and a second end of a filter cartridge adaptable to be coupled to a ...

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Номер записи: 49
15-02-2018 дата публикации

ASYMMETRIC UREAS AND MEDICAL USES THEREOF

Номер: US20180044293A1
Автор: GARCIA RUBIO Silvina, GIULIANO Claudio, Li Zhigang, PIETRA Claudio
Принадлежит:

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt or adduct thereof claim 1 , wherein R is aryl or heteroaryl.3. The compound of claim 1 , or a pharmaceutically acceptable salt or adduct thereof claim 1 , wherein R is selected from the group consisting of phenyl claim 1 , naphthalene claim 1 , tetrahydronaphthalenyl claim 1 , indenyl claim 1 , isoindenyl claim 1 , indanyl claim 1 , anthracenyl claim 1 , phenanthrenyl claim 1 , benzonaphthenyl claim 1 , fluorenyl claim 1 , indolizinyl claim 1 , pyrindinyl claim 1 , pyranopyrrolyl claim 1 , 4H-quinolizinyl claim 1 , purinyl claim 1 , naphthyridinyl claim 1 , pyridopyridinyl claim 1 , pteridinyl claim 1 , indolyl claim 1 , isoindolyl claim 1 , indoleninyl claim 1 , isoindazolyl claim 1 , benzazinyl claim 1 , phthalazinyl claim 1 , quinoxalinyl claim 1 , quinazolinyl claim 1 , benzodiazinyl claim 1 , benzopyranyl claim 1 , benzothiopyranyl claim 1 , benzoxazolyl claim 1 , indoxazinyl claim 1 , anthranilyl claim 1 , benzodioxolyl claim 1 , benzodioxanyl claim 1 , benzoxadiazolyl claim 1 , benzofuranyl claim 1 , isobenzofuranyl claim 1 , benzothienyl claim 1 , isobenzothienyl claim 1 , benzothiazolyl claim 1 , benzothiadiazolyl claim 1 , benzimidazolyl claim 1 , benzotriazolyl claim 1 , benzoxazinyl claim 1 , benzisoxazinyl claim 1 , and tetrahydroisoquinolinyl claim 1 , which is optionally independently substituted with from one to six substituents independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkoxy claim 1 , haloalkyl claim 1 , cyano claim 1 , —NO claim 1 , —OR claim 1 , hydroxy claim 1 , amino claim 1 , alkyl claim 1 , alkenyl claim 1 , cycloalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heterocycloalkyl claim 1 , heterocycloalkylalkyl claim 1 , ...

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Номер записи: 50
14-02-2019 дата публикации

Methods for preparing n-(4-fluorobenzyl)-n-(1-methylpiperidin-4-yl)-n'-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form

Номер: US20190047955A1
Автор: Andreas Philipp Boudier, Beat T. Weber, Marlon Carlos, Matthew J. Fleming, Mikael HILLGREN, Roger Olsson, Sagun Tandel
Принадлежит: Acadia Pharmaceuticals Inc

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —OR i or —NR 2a R 2b ; R 3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R 4 is substituted or unsubstituted aralkyl; X is —OR 22 or —NR 23 R 24 ; (wherein R 22 is hydrogen or substituted or unsubstituted C 1-6 alkyl and one of R 23 and R 24 is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R 21 is —OCH 2 CH(CH 3 ) 2 or F; Also disclosed herein is the tartrate salt of N-(4-fluoroben-zyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

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Номер записи: 51
25-02-2016 дата публикации

Substituted 1-arylethyl-4-acylaminopiperidine derivatives as opioid/alpha-adrenoreceptor modulators and method of their preparation

Номер: US20160052882A1
Автор: Hruby Victor J., Vardanyan Ruben S.
Принадлежит:

The invention provides compounds that bind with high affinities to the μ-, δ-and κ-opioid receptors and α-adrenoreceptor. In addition to providing these compounds with novel pharmacological binding properties, the invention also describes detailed novel methods for the preparation of representative compounds and a scheme for the synthesis of related compounds that bind to the opioid receptors and/or α-adrenoreceptor. 2. The compound of claim 1 , wherein the compound belongs to a series of N-(1-arylethylpiperidin-4-yl)acylamides.3. The compound of claim 1 , wherein the compound is N-(1-phenethylpiperidin-4-yl)propionamide.4. The compound of claim 1 , wherein the compound is N-(1-phenethylpiperidin-4-yl)propionamide oxalate.5. A process for preparing a compound of claim 1 , comprising the following steps:(a) reacting a cyclic ketone having a protecting group in a Grignard or Reformatsky reaction to obtain a first product;(b) reacting the product of step (a) in a Ritter reaction to obtain a second product; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) deprotecting the product of step (b) with acylation or alkylation to obtain a compound of .'}6. A process for preparing a compound of claim 1 , comprising the following steps:(a) reacting a cyclic ketone having a protecting group in a Strecker reaction to obtain a first product;(b) reacting the product of step (a) in a selective carbalkoxy group transformation to obtain a second product; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) deprotecting the product of step (b) with acylation or alkylation to obtain a compound of .'}7. A process for the preparation of N-(1-phenethylpiperidin-4-yl)propionamide claim 1 , comprising the following steps:(a) reacting phenethylpiperiding-4-one with hydroxylamine hydrochloride in ethanol in the presence of a base, to produce 1-phenethylpiperidin-4-one oxime;(b) reducing the oxime obtained in step (a) with iso-amyl alcohol and sodium metal to produce 1- ...

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Номер записи: 52
03-03-2016 дата публикации

Therapeutic Agent for Type 2 Diabetes

Номер: US20160060235A1
Автор: Inoue Kengo, Okawara Tadashi, Tomizawa Kazuhito, Wei Fanyan
Принадлежит:

An object of the present invention is to provide a novel therapeutic agent for a patient with type 2 diabetes, a cause of which is the abnormal synthesis of insulin attributed to the abnormal modification of tRNA(UUU) in pancreatic β cells having Cdkal1 gene mutation. The present inventors have used (1) a screening system using in which correct translation into luciferase requires frameshift resulting from mistranslation during protein translation, (2) a screening system using the pancreatic islet of Langerhans isolated from a pancreatic β cell-specific Cdkal1-deficient mouse, and (3) a screening system using a pancreatic β cell-specific Cdkal1-deficient mouse, and found that a compound represented by any of the following formulas (I) to (III) can serve as a therapeutic agent for a patient with type 2 diabetes with Cdkal1 gene mutation resulting in the reduced ability to secrete insulin. 3. The method for treating type 2 diabetes according to claim 1 , wherein the pharmaceutically acceptable salt is a salt with an acid selected from hydrochloric acid claim 1 , nitric acid claim 1 , sulfuric acid claim 1 , sulfonic acid having 1 to 10 carbon atoms claim 1 , a substituted or unsubstituted alkylcarboxylic acid having 1 to 6 carbon atoms claim 1 , and a substituted or unsubstituted dicarboxylic acid having 4 to 8 carbon atoms.4. The method for treating type 2 diabetes according to claim 3 , wherein the pharmaceutically acceptable salt is a salt with an acid selected from hydrochloric acid claim 3 , nitric acid claim 3 , methanesulfonic acid claim 3 , acetic acid claim 3 , levulinic acid claim 3 , lactic acid claim 3 , flurbiprofen claim 3 , ketoprofen claim 3 , oxalic acid claim 3 , fumaric acid claim 3 , and maleic acid.5. The method for treating type 2 diabetes according to claim 1 , wherein the type 2 diabetes is type 2 diabetes with a reduced ability to secrete insulin caused by Cdkal1 gene mutation.6. The method for treating type 2 diabetes according to claim 1 , ...

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Номер записи: 53
02-03-2017 дата публикации

Polymorphs of Lomitapide and its Salts

Номер: US20170057917A1
Автор: Mukunda Reddy Jambula, Muralidhara Reddy Dasari, Parthasaradhi Reddy Bandi, Rathnakar Reddy Kura, Vamsi Krishna Bandi
Принадлежит:

The present invention provides novel polymorphs of Lomitapide, process for their preparation and pharmaceutical compositions comprising them. The present invention also provides a novel polymorph of Lomitapide mesylate, process for its preparation and pharmaceutical compositions comprising it. 1. Crystalline Lomitapide , wherein designated as Form 1 , Form 2.2. Form 1 of Crystalline Lomitapide of claim 1 , having a Powder X-ray diffractogram as shown in .3. Form 1 of Crystalline Lomitapide of claim 1 , characterized by peaks in the powder x-ray diffraction spectrum having 2θ angle positions at about 7.7 claim 1 , 15.5 claim 1 , 17.3 claim 1 , 20.2 claim 1 , 21.4 and 21.9±0.2 degrees.4. The process for the preparation of the Form 1 of Crystalline Lomitapide of claim 1 , which comprises:a) suspending Lomitapide in a hydrocarbon solvent;b) heating the contents obtained in step (a) above 50° C.;c) adding a ketonic solvent to the solution;d) adding a hydrocarbon solvent to the solution; ande) isolating Lomitapide crystalline Form 1.5. The process as claimed in claim 4 , wherein the hydrocarbon solvent is preferably selected from the group consisting of cyclohexane claim 4 , hexane claim 4 , heptane claim 4 , n-hexane claim 4 , n-heptane claim 4 , toluene claim 4 , xylene or mixture thereof and more preferably heptane.6. The process as claimed in claim 4 , wherein the ketonic solvent is preferably selected from the group consisting of acetone claim 4 , methyl ethyl ketone claim 4 , diethyl ketone claim 4 , methyl isobutyl ketone or mixture thereof and more preferably acetone.7. Form 2 of Crystalline Lomitapide of claim 1 , having a Powder X-ray diffractogram as shown in .8. Form 2 of Crystalline Lomitapide of claim 1 , characterized by peaks in the powder x-ray diffraction spectrum having 2θ angle positions at about 5.5 claim 1 , 10.9 claim 1 , 13.5 claim 1 , 13.7 claim 1 , 18.2 claim 1 , 19.0 and 22.0±0.2 degrees.9. The process for the preparation of the Form 2 of ...

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Номер записи: 54
05-03-2015 дата публикации

Treating Neuropathic Pain with Seh Inhibitors

Номер: US20150065540A1
Автор: Hammock Bruce D., Inceoglu Bora, Lee Kin Sing, Wagner Karen
Принадлежит:

Provided are methods for treating, reducing, alleviating, and/or inhibiting neuropathic pain by orally, intravenously or intrathecally administering an effective amount of an inhibitor of soluble epoxide hydrolase (“sEH”), to a patient in need thereof. The neuropathic pain treated is selected from the group consisting of post-herpetic neuralgia, trigeminal neuralgia, focal peripheral nerve injury, and anesthesia dolorosa, central pain due to stroke or mass lesion, spinal cord injury, or multiple sclerosis, and peripheral neuropathy due to diabetes, HIV, or chemotherapy. 2. The method of claim 1 , wherein each Ris selected from the group consisting of halogen claim 1 , Chaloalkyl claim 1 , and Chaloalkoxy.3. The method of claim 1 , wherein each Ris selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CF claim 1 , CFCF claim 1 , CF(CF) claim 1 , CH(CF) claim 1 , and OCF.4. The method of claim 1 , wherein each Ris selected from the group consisting of Cl claim 1 , CF claim 1 , and OCF.5. The method of claim 1 , wherein each Ris selected from the group consisting of CF claim 1 , and OCF.6. The method of claim 1 , wherein Ris selected from the group consisting 2 of Calkyl claim 1 , Chaloalkyl claim 1 , and cycloalkyl having 3-6 ring members.7. The method of claim 1 , wherein Ris selected from the group consisting of ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , sec-butyl claim 1 , iso-butyl claim 1 , tert-butyl claim 1 , pentyl claim 1 , pent-2-yl claim 1 , pent-3-yl claim 1 , iso-pentyl claim 1 , neopentyl claim 1 , hexyl claim 1 , CF claim 1 , CHCF claim 1 , (CH)CF claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl and cyclohexyl.8. The method of claim 1 , wherein Ris selected from the group consisting of isopropyl claim 1 , sec-butyl claim 1 , (S)-sec-butyl claim 1 , pent-3-yl claim 1 , and cyclopropyl.9. The method of claim 1 , wherein Ris selected from the group consisting of isopropyl and (S)- ...

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Номер записи: 55
22-05-2014 дата публикации

SELECTIVE SEROTONIN 2A/2C RECEPTOR INVERSE AGONISTS AS THERAPEUTICS FOR NEURODEGENERATIVE DISEASES

Номер: US20140140982A1
Автор: ANDERSSON Carl-Magnus A., BRANN Mark R., DAVIS Robert E., Uldam Allan K., WEINER David M.
Принадлежит: ACADIA Pharmaceuticals Inc.

Behavioral pharmacological data with the compound of formula (I), a novel and selective 5HT2A/2C receptor inverse agonist, demonstrate in vivo efficacy in models of psychosis and dyskinesias. This includes activity in reversing MK-801 induced locomotor behaviors, suggesting that this compound may be an efficacious anti-psychotic, and activity in an MPTP primate model of dyskinesias, suggesting efficacy as an anti-dyskinesia agent. These data support the hypothesis that 5HT2A/2C receptor inverse agonism may confer antipsychotic and anti-dyskinetic efficacy in humans, and indicate a use of the compound of formula (I) and related agents as novel therapeutics for Parkinson's Disease, related human neurodegenerative diseases, and psychosis. 186.-. (canceled)88. The method of claim 87 , wherein the salt is a tartrate salt.89. The method of claim 87 , wherein the salt is a hydrochloride salt.90. The method of claim 87 , wherein the amount of the compound of formula (I) claim 87 , or a pharmaceutically acceptable salt thereof claim 87 , is from about 0.001 mg to about 50 mg.91. The method of claim 87 , wherein the amount of the compound of formula (I) claim 87 , or a pharmaceutically acceptable salt thereof claim 87 , is from about 1 mg to about 10 mg.92. The method of claim 87 , wherein the amount of the compound of formula (I) claim 87 , or a pharmaceutically acceptable salt thereof claim 87 , is about 10 mg.93. The method of claim 87 , wherein the amount of the compound of formula (I) claim 87 , or a pharmaceutically acceptable salt thereof claim 87 , is about 25 mg.94. The method of claim 87 , wherein the amount of the compound of formula (I) claim 87 , or a pharmaceutically acceptable salt thereof claim 87 , is about 50 mg.95. The method of claim 87 , wherein the compound of formula (I) is administered daily.96. The method of claim 87 , wherein the compound of formula (I) is administered once daily.97. The method of claim 87 , wherein the neurodegenerative disease is ...

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Номер записи: 56
27-02-2020 дата публикации

PIPERIDINYL-3-(ARYLOXY)PROPANAMIDES AND PROPANOATES

Номер: US20200061041A1
Автор: Cheruvallath Zacharia, Green Jason, Johnson Ben, Schleicher Kristin, Sun Huikai, Tang Mingnam
Принадлежит:

Disclosed are compounds of Formula 1, 2. The compound or pharmaceutically acceptable salt according to claim 1 , wherein Xis CR claim 1 , Xis CR claim 1 , Xis CR claim 1 , and Xis CR.3. The compound or pharmaceutically acceptable salt according to claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare each independently selected from(a) hydrogen, halo, and cyano; and{'sub': 1-4', '3-6', '1-4, '(b) Calkyl, Ccycloalkyl, and Calkoxy, each substituted with 0 to 3 optional substituents independently selected from halo.'}46-. (canceled)7. The compound or pharmaceutically acceptable salt according to claim 1 , wherein Xis N claim 1 , Xis CR claim 1 , Xis CR claim 1 , and Xis CR.8. The compound or pharmaceutically acceptable salt according to claim 7 , wherein R claim 7 , R claim 7 , and Rare each independently selected from(a) hydrogen, halo, and cyano; and{'sub': 1-4', '3-6', '1-4, '(b) Calkyl, Ccycloalkyl, and Calkoxy, each substituted with 0 to 3 optional substituents independently selected from halo.'}9.10.11.12. The compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris selected from(a) hydrogen, halo, hydroxy, and cyano; and{'sub': 1-4', '3-6', '1-4, '(b) Calkyl, Ccycloalkyl, and Calkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, oxo, and phenyl which is substituted with 0 to 3 optional substituents independently selected from halo.'}1314-. (canceled)15. The compound or pharmaceutically acceptable salt according to claim 1 , wherein Rand Rare each independently selected from fluoro and methyl or together with the carbon atom to which they are attached form a cyclopropan-1 claim 1 ,1-diyl or a cyclobutan-1 claim 1 ,1-diyl.16. The compound or pharmaceutically acceptable salt according to claim 1 , wherein each of Rand Ris methyl.17. The compound or pharmaceutically acceptable salt according to claim 1 , wherein L is NR.18. (canceled)19. The compound or pharmaceutically acceptable salt according ...

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Номер записи: 57
27-02-2020 дата публикации

AMINE-CONTAINING TRANSFECTION REAGENTS AND METHODS FOR MAKING AND USING SAME

Номер: US20200061197A1
Автор: Angrish Parul, DE MOLLERAT DU JEU Xavier, WIEDERHOLT Kristin, Yang Zhiwei
Принадлежит:

There are provided for herein novel amine-containing transfection compounds and methods for making and using same. The compounds are generally obtained by reacting a primary amine with an unsaturated compound. Transfection complexes made using the amine-containing transfection compounds in combination with additional compounds to encapsulate biologically active agents such as nucleic acids are also provided for herein. Methods of using the transfection complexes for the in vivo or in vitro delivery of biologically active agents are also described. The transfection complexes of the present invention are highly potent, thereby allowing effective modulation of a biological activity at relatively low doses compared to analogous transfection compounds known in the art. 2. The compound of claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein each of Rand Ris independently selected from the group consisting of substituted or unsubstituted claim 1 , branched or unbranched alkyl or alkenyl groups having between 3 and about 20 carbon atoms claim 1 , and between 0 and 4 double bonds.3. (canceled)5. (canceled)78-. (canceled)9. The compound of claim 6 , or pharmaceutically acceptable salts thereof claim 6 , wherein each Ris independently selected from the group consisting of substituted or unsubstituted claim 6 , branched or unbranched alkyl or alkenyl groups having between 3 and about 20 carbon atoms claim 6 , and between 0 and 4 double bonds.1012-. (canceled)15. The method of claim 14 , wherein each of Rand Ris independently selected from the group consisting of substituted or unsubstituted claim 14 , branched or unbranched alkyl or alkenyl groups having between 3 and about 20 carbon atoms claim 14 , and between 0 and 4 double bonds.1617-. (canceled)19. (canceled)20. The method of claim 14 , wherein each of R claim 14 , R claim 14 , Rand Ris hydrogen and each of Y and Z is C═O.2122-. (canceled)24. The transfection complex of claim 23 , or pharmaceutically ...

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Номер записи: 58
24-03-2022 дата публикации

High-throughput method to rapidly add chemical moieties to a small molecule library

Номер: US20220089537A1
Автор: Angela N. Koehler, Brice CURTIN, Catherine HENRY, Chia-Fu Chang, Christina Woo, Jasmin KRUELL, Sebastian POMPLUN
Принадлежит: Harvard College, Massachusetts Institute of Technology

Organic compounds for target identification, drug discovery, chemical library production, high-throughput screening, fluorophore conjugation, chemiluminescent compound conjugation, creation of proximity induced modulators (e.g., protein degraders)/chimeric molecules, or a combination thereof are described. The compounds can contain small molecule moieties for identification of their potential targets; an isocyanate, photoactivatable groups; chemical moieties for enrichment and detection of target-small molecule moiety interactions; proximity induced modulator element; fluorophores; chemiluminescent groups; or combinations thereof.

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Номер записи: 59
18-03-2021 дата публикации

ARYL HETEROCYCLIC PIPERIDINONE FORMYL PEPTIDE 2 RECEPTOR AND FORMYL PEPTIDE 1 RECEPTOR AGONISTS

Номер: US20210078971A1
Автор: Chattopadhyay Amit Kuma, Shirude Pravin Sudhakar, Wurtz Nicholas R.
Принадлежит:

The disclosure relates to compounds of formula (I), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, and related diseases. 2. A compound of where{'sup': '1', 'Aris phenyl, pyrazinyl or pyridinyl and is substituted with 1-3 substituents selected from cyano, halo, alkyl, fluoroalkyl, haloalkyl, alkoxy, fluoroalkoxy, alkylthio, and alkylsulfonyl;'}{'sup': '2', 'Aris phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, fluoroalkyl, alkoxy, and haloalkoxy;'}{'sup': 1', '2', '3', '2', '3', '2', '3, 'Ris cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahyrofuranyl, or tetrahydropyranyl, and is substituted with 0-2 substituents selected from cyano, alkyl, fluoroalkyl, hydroxyalkyl, alkoxyalkyl, ((R)(R)N)alkyl, hydroxy, alkoxy, (R)(R)N, (R)(R)NCO, and Ara;'}{'sup': '2', 'Ris hydrogen, alkyl, alkylcarbonyl, or alkylsulfonyl;'}{'sup': '3', 'Ris hydrogen or alkyl;'}{'sup': 2', '3, 'or NRRtaken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, and is substituted with 0-3 substituents selected from fluoro, alkyl, fluoroalkyl, alkoxy, and haloalkoxy; and'}X is hydrogen, fluoro, hydroxy, or alkoxy;or a pharmaceutically acceptable salt thereof.3. A compound of where Aris phenyl claim 1 , pyrazinyl or pyridinyl and is substituted with 1-3 substituents selected from cyano claim 1 , halo claim 1 , alkyl claim 1 , fluoroalkyl claim 1 , alkoxy claim 1 , fluoroalkoxy claim 1 , alkylthio claim 1 , and alkylsulfonyl.4. A compound of where Aris phenyl substituted with 0-3 substituents selected from cyano claim 1 , halo claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , and fluoroalkoxy.5. A compound of where Ris cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , tetrahyrofuranyl ...

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Номер записи: 60
22-03-2018 дата публикации

HYDROBROMIDE SALT OF N-(4-CHLORO-2-HYDROXY-3-((3S)-3-PIPERIDINYLSULFONYL)PHENYL-N'-(3-FLUORO-2-METHYLPHENYL)UREA

Номер: US20180079722A1
Автор: SANDERSON Francis Dominic, VALLANCE Sarah Mary
Принадлежит:

A compound which is the hydrobromide salt of N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments. 1. A pharmaceutical composition in an oral dosage form comprising a hemihydrate of the hydrobromide salt of N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea and one or more pharmaceutically acceptable carriers , diluents or excipients ,wherein the oral dosage form is selected from the group consisting of capsule, tablet, powder, granule, solution, suspension in aqueous or non-aqueous liquids, edible forms, whips, oil-in-water liquid emulsion and water-in-oil liquid emulsion.2. The pharmaceutical composition according to claim 1 , wherein the oral dosage form is a tablet or capsule.3. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of ethanol claim 1 , glycerol claim 1 , water.4. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable carrier is selected from starch or mannitol.5. The pharmaceutical composition according to claim 1 , wherein a pharmaceutically acceptable excipient is a lubricant selected from the group consisting of sodium oleate claim 1 , sodium stearate claim 1 , magnesium stearate claim 1 , sodium benzoate claim 1 , sodium acetate claim 1 , sodium chloride.6. The pharmaceutical composition according to claim 1 , wherein a pharmaceutically acceptable excipient is a disintegrator selected from the group consisting of starch claim 1 , methyl cellulose claim 1 , agar claim 1 , bentonite claim 1 , and xanthan gum.7. The pharmaceutical composition according to claim 1 , wherein a pharmaceutically acceptable excipient is a binder selected from ...

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Номер записи: 61
24-03-2016 дата публикации

POLYMORPHIC FORMS OF LOMITAPIDE AND ITS SALTS AND PROCESSES FOR THEIR PREPARATION

Номер: US20160083345A1
Автор: AGRAVAT Sureshkumar Narbheram, DESAI Sanjay Jagdish, KHERA Brij, PATEL Jagdish Maganlal, SHAH Harshita Bharatkumar, UPADHYAY Arunkumar Shyam Narayan
Принадлежит: CADILA HEALTHCARE LIMITED

The present invention relates to various polymorphic forms of lomitapide or its salts and processes for preparation thereof. The present invention provides Lomitapide mesylate in solid amorphous form and process for preparation thereof. The invention also provides an amorphous solid dispersion of lomitapide mesylate. Further, various crystalline forms of lomitapide mesylate like A, B and C and process for preparation thereof are provided. The invention also provides crystalline forms of lomitapide free base, in particular Form I and Form-II and their preparation. The invention further provides compositions comprising various forms of lomitapide and its salts. 1. Lomitapide mesylate in solid amorphous form.2. The amorphous form according to having less than about 0.5% residual solvents when measured by GC and having a moisture content less than 5% wt/wt.3. The amorphous form according to having a purity of about 98% or more claim 1 , as measured by area percentage of HPLC.4. The amorphous form according to which is stable for a period of at least three months alter exposure to a relative humidity of 75% at 40° C. or a relative humidity of 60% at 25° C. claim 1 , and does not change to any crystalline form and contains less than about 0.5% wt/wt total impurities.5. The lomitapide mesylate according to having particle size distribution as characterized by 90% particles having particle size (D) of about 250 μm or less claim 1 , 50% particles having particle size (D) of about 100 μm or less claim 1 , and 10% particles having particle size (D) of about 50 μm or less.6. A process for the preparation of the amorphous form of lomitapide mesylate according to claim 1 , the process comprising:(a) providing a solution of lomitapide mesylate in one or more solvents; and(b) obtaining the amorphous form of lomitapide mesylate by the removal of the solvents, or(a) providing a solution of lomitapide free base in one or more solvents;(b) adding methane sulfonic acid to the solution; ...

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Номер записи: 62
31-03-2022 дата публикации

ANTIBIOTIC AMMONIUM COMPOUNDS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS

Номер: US20220098148A1
Автор: Cunningham Ashley, DAVIES Bryan, McHARDY Stanton, Wang Hua-Yu
Принадлежит: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM

The present disclosure provides ammonium compounds, e.g., compounds according to Formula I as set forth herein, which are useful as antimicrobial agents. Methods for the treatment of bacterial infections and associated conditions, e.g., gastrointestinal conditions, are also described, as well as methods for altering the microbiome of subjects such as humans. 2. The compound of claim 1 , wherein at least one of Rand Ris Calkoxy.34-. (canceled)5. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris halogen.6. The compound of claim 1 , wherein Rand Rare independently selected from the group consisting of H and halogen.8. The compound of claim 1 , wherein Ris selected from the group consisting of Calkyl and -L-R.910-. (canceled)11. The compound of claim 8 , wherein Ris selected from the group consisting of Ccycloalkyl and Caryl.12. The compound of claim 1 , wherein;{'sup': 2', '3, 'sub': '1-6', 'Rand Rare each Calkyl;'}{'sup': 2', '3, 'Rand Rare taken together with the nitrogen to which they are attached to form 3- to 10-membered heterocyclyl: or'}{'sup': '2', 'Ris taken together with the nitrogen to which it is attached and Z to form 3- to 10-membered heterocyclyl.'}1314-. (canceled)15. The compound of claim 12 , wherein Ris Calkyl.16. The compound of claim 1 , wherein Y is-NRSO—.17. The compound of claim 1 , wherein Y is selected from the group consisting of —OC(O)— and —NRC(O)—.18. The compound of claim 1 , wherein A is bromide.23. A pharmaceutical composition comprising a compound according to and pharmaceutically acceptable excipient.2534-. (canceled)35. The method of claim 24 , wherein the bacterial infection is caused by Gram-positive bacteria.36C. difficile, S. aureus, StreptococcusEnterococcusC. diphtheriae, L. monocytogenes. The method of claim 35 , wherein the Gram-positive bacteria are selected from the group consisting of spp. claim 35 , spp. claim 35 , claim 35 , and combinations thereof.37. The method ...

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Номер записи: 63
26-03-2015 дата публикации

COMPOSITIONS AND METHODS FOR TREATING CANCER

Номер: US20150087628A1
Автор: Ostrem Jonathan, Peters Ulf, Shokat Kevan M.
Принадлежит:

K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer. 1. A compound having the formula:{'br': None, 'sup': 1', '1', '2', '3, 'R-L-L-L-E'}wherein,{'sup': '1', 'Ris a Switch 2-Binding Pocket binding moiety;'}{'sup': '1', 'Lis a bond or a divalent radical chemical linker;'}{'sup': '2', 'Lis a bond or a divalent radical chemical linker;'}{'sup': '3', 'Lis a bond or a divalent radical chemical linker;'}E is an electrophilic chemical moiety capable of forming a covalent bond with a K-Ras cysteine residue or a K-Ras aspartate residue.2. The compound of claim 1 , wherein Ris hydrogen claim 1 , substituted or unsubstituted alkyl claim 1 , substituted or unsubstituted heteroalkyl claim 1 , substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted heterocycloalkyl claim 1 , substituted or unsubstituted aryl claim 1 , or substituted or unsubstituted heteroaryl.36.-. (canceled)9. (canceled)1214.-. (canceled)16. The compound of claim 1 , wherein E comprises a substituted or unsubstituted vinyl sulfone moiety claim 1 , substituted or unsubstituted vinyl sulfonamide moiety claim 1 , substituted or unsubstituted fluoro(C-C)alkylketone moiety claim 1 , substituted or unsubstituted chloro(C-C)alkylketone moiety claim 1 , substituted or unsubstituted acrylamide moiety claim 1 , substituted or unsubstituted disulfide moiety claim 1 , substituted or unsubstituted thiol moiety claim 1 , substituted or unsubstituted phosphonate moiety claim 1 , substituted or unsubstituted aldehyde moiety claim 1 , substituted or unsubstituted enone moiety claim 1 , substituted or unsubstituted diazomethylketone moiety claim 1 , substituted or unsubstituted diazomethylamide moiety claim 1 , substituted or unsubstituted cyanocyclopropyl carboxamide moiety claim 1 , substituted or unsubstituted epoxide moiety claim 1 , substituted or unsubstituted epoxyketone moiety claim 1 , substituted or ...

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Номер записи: 64
12-06-2014 дата публикации

PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF

Номер: US20140163230A1
Автор: Boyd Alistair, Cherryman Janette, Dedhiya Mahendra G., Golden Michael, Kalyan Yuriy B., Lawton Graham Richard, Milne David, Phillips Andrew, Racha Saibaba, Ronsheim Melanie Simone, TELFORD Alexander, Zhou Shao Hong
Принадлежит: FOREST LABORATORIES HOLDINGS LTD.

The present invention relates to compounds and processes for preparing compounds of Formula (I), 2. The process of claim 1 , wherein R1 claim 1 , R2 and R7 are hydrogen and R3 is OSOH.3. The process of claim 1 , wherein R1 is piperidinyl claim 1 , R2 and R7 are hydrogen and R3 is OSOH.4. The process of claim 1 , wherein R4 is benzyloxy.5. The process of claim 1 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.6. The process of claim 1 , wherein R5 is allyl or trialkylsilyl and R6 is hydrogen.7. The process of claim 1 , comprising treating the compound of Formula (III) with 9-fluorenylmethoxycarbonyl.8. The process of claim 1 , comprising treating the compound of Formula (III) with N claim 1 ,N-carbonyl diimidazole.9. The process of claim 1 , further comprising treating the compound formed after treatment of compound of Formula (III) with a SOcomplex.10. The process of claim 1 , wherein the compound of Formula (I) is trans-7-oxo-6-(sulphooxy)-1 claim 1 ,6-diazabicyclo[3 claim 1 ,2 claim 1 ,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof.11. The process of claim 1 , wherein the compound of Formula (I) is sodium ({[(2S claim 1 ,5R)-2-carbamoyl-7-oxo-1 claim 1 ,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulphonyl)oxidanide.12. The process of claim 1 , wherein the compound of Formula (II) is benzyl (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate.13. The process of claim 1 , wherein the compound of Formula (III) is (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide.14. The process of claim 13 , comprising treating (2S claim 13 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide to prepare (2S claim 13 ,5R)-6-(benzyloxy)-7-oxo-1 claim 13 ,6-diazabicyclo[3.2.1]octane-2-carboxamide.16. The compound of claim 15 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.17. The compound of claim 15 , wherein R5 is allyl or trialkylsilyl and R6 and R7 are hydrogen.18. The compound of claim 15 , wherein R5 is benzyloxy and R1 claim ...

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Номер записи: 65
31-03-2016 дата публикации

PIPERIDINE DERIVATIVE, LIQUID CRYSTAL COMPOSITION AND LIQUID CRYSTAL DISPLAY DEVICE

Номер: US20160090534A1
Автор: GOTOH YASUYUKI, Kimura Keiji
Принадлежит:

To provide a compound having an effect for preventing photolysis of a liquid crystal composition, and having a high solubility in the liquid crystal composition, a liquid crystal composition containing the compound, and a liquid crystal display device including the composition. The compound is represented by formula (1), a liquid crystal composition contains the compound, and a liquid crystal display device includes the composition: 6. The compound according to , wherein , in formulas (1a) to (1s) described in , Rin formulas (Q-1) to (Q-3) is hydrogen , —O. , —OH , alkyl having 1 to 10 carbons or alkoxy having 1 to 10 carbons.9. A liquid crystal composition claim 1 , containing at least one compound according to .14. The liquid crystal composition according to claim 9 , further containing at least one of a polymerizable compound claim 9 , a polymerization initiator claim 9 , a polymerization inhibitor claim 9 , an optically active compound claim 9 , an antioxidant claim 9 , an ultraviolet light absorber claim 9 , a light stabilizer claim 9 , a heat stabilizer and an antifoaming agent.15. A liquid crystal display device claim 9 , including at least one of the liquid crystal composition according to . The present invention relates to a piperidine derivative, a liquid crystal composition and a liquid crystal display device. More specifically, the invention relates to an isopropylpiperidine derivative, a liquid crystal composition that contains the compound and has a positive or negative dielectric anisotropy, and a liquid crystal display device including the composition.In a liquid crystal display device, a classification based on an operating mode for liquid crystal molecules includes a phase change (PC) mode, a twisted nematic (TN) mode, a super twisted nematic (STN) mode, an electrically controlled birefringence (ECB) mode, an optically compensated bend (OCB) mode, an in-plane switching (IPS) mode, a vertical alignment (VA) mode, a fringe field switching (FFS) mode, ...

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Номер записи: 66
21-03-2019 дата публикации

NON-HALOGENATED FLAME RETARDANT HINDERED AMINE LIGHT STABILIZER CROSS-LINKERS

Номер: US20190085149A1
Автор: King Scott B., Kobilka Brandon M., Kuczynski Joseph, Wertz Jason T.
Принадлежит:

A process a process of forming a non-halogenated flame retardant (FR) hindered amine light stabilizer (HALS) cross-linker is disclosed. The process includes forming a mixture that includes a first molecule having a hindered amine group. The first molecule corresponds to a functionalized 2,2,6,6-tetramethylpiperidine (TMP) molecule. The process also includes forming the non-halogenated FR HALS cross-linker via a chemical reaction of the first molecule a second molecule. The second molecule includes a phosphoryl group, a chloride group, and at least one cross-linkable (CL) moiety. 112.-. (canceled)14. The process of claim 13 , wherein the at least one allyl group includes a single allyl group.15. The process of claim 13 , wherein the at least one allyl group includes two allyl groups.1620.-. (canceled) Hindered amine light stabilizer (“HALS”) molecules may be added to a polymer in order to protect the polymer from radiation damage, such as ultraviolet (UV) degradation of the polymer. HALS molecules are believed to provide protection from radiation damage by terminating photo-oxidation processes in polymers through chemical reaction with free radical and peroxide intermediates. A common approach to render a polymer flame retardant is by incorporation of additives such as halogenated (e.g., brominated) materials. In some cases, brominated flame retardant additives may release bromine radicals that may react directly with the HALS molecules or may abstract a hydrogen from the polymer matrix and deactivate the HALS molecules through an acid-base reaction. The result is loss of light stabilization and rapid UV degradation of the unprotected polymer.According to an embodiment, a process of forming a non-halogenated flame retardant (FR) hindered amine light stabilizer (HALS) cross-linker is disclosed. The process includes forming a mixture that includes a first molecule having a hindered amine group. The first molecule corresponds to a functionalized 2,2,6,6- ...

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Номер записи: 67
30-03-2017 дата публикации

PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO

Номер: US20170088507A1
Автор: Boruwa Joshodeep, Hunter James E., Iyer Pravin S., Lo William C., Patny Akshay, Watson Gerald B.
Принадлежит: DOW AGROSCIENCES LLC

This document discloses molecules having the following formula (“Formula One”): 2. A molecule according to wherein R1 is selected from H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , NO claim 1 , methyl claim 1 , ethyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , halomethyl claim 1 , haloethyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , methoxy claim 1 , ethoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , halomethoxy claim 1 , haloethoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , and halo(C)alkoxy.3. A molecule according to wherein R2 is selected from H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , NO claim 1 , methyl claim 1 , ethyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , halomethyl claim 1 , haloethyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , halo(C)alkyl claim 1 , methoxy claim 1 , ethoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , (C)alkoxy claim 1 , halomethoxy claim 1 , haloethoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , halo(C)alkoxy claim 1 , and halo(C)alkoxy.4. A molecule according to wherein R3 is selected from H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , NO claim 1 , methyl claim 1 , ethyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , (C)alkyl claim 1 , halomethyl claim 1 , ...

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Номер записи: 68
19-03-2020 дата публикации

PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED 3-AMINOPIPERIDINE

Номер: US20200087257A1
Автор: Andrushko Vasyl, Kantor Mark, Meier Viktor, Reuter Karl, Stolz Florian, Wedel Tobias
Принадлежит: REUTER CHEMISCHE APPARATEBAU KG

The present invention relates to a process for the preparation of enantiomerically enriched 3-aminopiperidine, as in particular of its R-enantiomer (R)-3-aminopiperidine. The invention also relates to an enantiomerically enriched intermediate of said process and to specific acid-addition salts of 3-aminopiperidine (hereinafter also APIP) that are useful for obtaining a single enantiomer of APIP, and to crystalline (R)-3-aminopiperidine-dihydrochloride-monohydrateand crystalline (S)-3-aminopiperidine-dihydrochloride-monohydrate. 2. The process according to claim 1 , wherein the carboxylic acid A is selected from (S)-2-phenyl sulfonylamino-propionic acid claim 1 , (S)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 1 , (S)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 1 , (R)-2-(3-phenylureido)-propionic acid and (R)-2-(3-(4-chlorophenyl)ureido)-propionic acid.3. A process for enantiomeric enrichment of 3-aminopiperidine with regard to its S-enantiomer claim 1 , the process comprising the fractional crystallization of 3-aminopiperidine in the form of its acid-addition salt with a chiral carboxylic acid A from a solution claim 1 , suspension or emulsion containing a mixture of the enantiomers of 3-aminopiperidine claim 1 , in particular a racemic mixture of the enantiomers of 3-aminopiperidine claim 1 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'where the chiral carboxylic acid A is the compound of the formula A, as defined in , where the chiral carboxylic acid A has an enantiomeric excess with regard to one of its enantiomers.'}4. The process according to claim 3 , wherein the carboxylic acid A is selected from (R)-2-phenyl sulfonylamino-propionic acid claim 3 , (R)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 3 , (R)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 3 , (S)-2-(3-phenylureido)-propionic acid and (S)-2-(3-(4-chlorophenyl)ureido)-propionic acid.5. The acid-addition salt of 3-aminopiperidine with the chiral carboxylic acid A ...

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Номер записи: 69
12-05-2022 дата публикации

PROCESSES FOR PREPARING (3R,4R)-1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE OR A SALT THEREOF AND PROCESSES FOR PREPARING TOFACITINIB USING THE SAME

Номер: US20220144774A1
Автор: CHO Sung-Hee, CHOI Ji-Hye, HWANG Hyo-Ick, JO Ik-Su, KIM Sang-won, Kwon Kyoung-Chan, LEE Doo-Byung, LEE Kyeong-Sill, Lee Su-young, OH Sang-Ho
Принадлежит: YUHAN CORPORATION

Provided are a novel process for preparing (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine or a salt thereof, which is an intermediate useful for the preparation of tofacitinib, an intermediate used in the process, i.e., isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate dibenzoyl-L-tartrate, an intermediate, having excellent stability, useful for the preparation of tofacitinib, i.e., (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine acetate, and a process for preparing tofacitinib or a pharmaceutically acceptable salt thereof. 1. A process for preparing (3R ,4R)-1-benzyl-N ,4-dimethylpiperidin-3-amine or a salt thereof , the process of which comprises:(a) reacting racemic methyl (1-benzyl-4-methylpiperidin-3-yl)carbamate and dibenzoyl-L-tartaric acid by heating under reflux in a solvent selected from the group consisting of isopropanol, an aqueous solution of isopropanol, and a mixed solvent of isopropanol and an organic solvent, followed by cooling to prepare isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate dibenzoyl-L-tartrate; and(b) reacting the isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate dibenzoyl-L-tartrate prepared in Step (a) with a base to convert to methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate; and then reducing the methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate to prepare (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine.2. The process according to claim 1 , wherein the mixed solvent of isopropanol and an organic solvent is a mixed solvent of isopropanol and an organic solvent selected from the group consisting of methanol claim 1 , ethanol claim 1 , n-propanol claim 1 , acetone claim 1 , methylethylketone claim 1 , methyl acetate claim 1 , ethyl acetate claim 1 , tetrahydrofuran claim 1 , 2-m ethyltetrahydrofuran and acetonitrile.3. The process according to claim 1 , wherein Step (a) further comprises recrystallizing the isopropanol ...

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Номер записи: 70
14-04-2016 дата публикации

AN IMPROVED PROCESS FOR THE PREPARATION OF (3R,4R)-(1-BENZYL-4-METHYLPIPERIDIN-3-YL)-METHYLAMINE

Номер: US20160102057A1
Автор: Bonde Nilesh L., Das Arijit, Kekan Ankush Sampat, Patil Yogesh Subhash, Sathe Dhananjay G.
Принадлежит:

The present invention is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: 1. A process for the preparation of (3R ,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine (Formula IIa) comprising:(i) N-acylation of 3-Amino-4-methyl pyridine (Formula III) with alkyl, aryl or substituted aryl acid chloride or acid anhydride to prepare a compound of the Formula IVa and optionally isolating it;(ii) quarternization of Nitrogen of the Pyridine system in a compound of the Formula IVa, using benzyl or substituted aryl benzyl halide in an organic solvent to prepare a compound of the Formula Va and optionally isolating it;(iii) partial reduction of a compound of the Formula Va to produce 1,2,5,6-Tetrahydropyridine system of a compound of the Formula VIa in presence of a reducing agent or any alkali metal borohydride agent in a suitable solvent, at an ambient temperature;(iv) hydrolysis of 1,2,5,6-Tetrahydropyridine system of a compound of the Formula VIa in presence of an acid or mixture of acids to prepare a compound of the Formula VIIa at an ambient temperature;(v) reductive amination of a compound of the Formula VIIa using Methylamine in presence of any Lewis acid in an organic solvent or an aqueous solvent or mixture(s) thereof followed by reduction using any reducing agent or any alkali metal borohydride derivatives to prepare a compound of the Formula VIIIa at an ambient temperature; and(vi) further resolution of a compound of the formula VIIIa in presence of any resoluting agent in an organic solvent or an aqueous solvent or mixture(s) thereof to prepare the compound of Formula IIa.2. The process for the preparation of (1-Benzyl-4-methylpiperidin-3-yl)-methylamine of the Formula VIIIa comprising the process as claimed in (i) to (v).3. The process of claim 1 , wherein the alkyl claim 1 , aryl or substituted aryl acid anhydride of step (i) comprises an anhydride of C1-10 acids.41. The process ...

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Номер записи: 71
12-04-2018 дата публикации

NOVEL KAPPA OPIOID LIGANDS

Номер: US20180099954A1
Автор: Guerrero Miguel A., Roberts Edward, ROSEN Hugh, Urbano Mariangela
Принадлежит:

The invention provides novel ligands of Kappa (κ) opioid receptors, such as can be used to modulate a Kappa opioid receptor. Methods of synthesis and methods of use are also provided. Compounds of the invention can be used therapeutically in the treatment of dissociative disorders or pain, or to provide neuroprotection, or to induce diuresis, or to modulate the immune system, or for treatment of one or more of an affective disorders comprising depression or stress/anxiety; an addictive disorder; alcoholism, epilepsy; a cognition deficiency; schizophrenia; Alzheimer's disease; or pain. 120-. (canceled)22. The method of claim 21 , wherein the condition is an affective disorder.23. The method of claim 22 , wherein the affective disorder is depression or anxiety.24. The method of claim 23 , wherein the anxiety is stress related anxiety.25. The method of claim 21 , wherein the condition is an addictive disorder.26. The method of claim 21 , wherein the condition is alcoholism.27. The method of claim 21 , wherein the condition is epilepsy.28. The method of claim 21 , wherein the condition is a cognition deficiency.29. The method of claim 21 , wherein the condition is schizophrenia.30. The method of claim 21 , wherein the condition is Alzheimer's disease.31. The method of claim 21 , wherein the condition is pain.32. The method of claim 21 , wherein Y is H.33. The method of claim 21 , wherein Y is (C-C)alkyl.34. The method of claim 21 , wherein Y is halo.35. The method of claim 21 , wherein Z is 3-methyl-1 claim 21 ,2 claim 21 ,4-oxadiazol-5-yl claim 21 , 3-ethyl-1 claim 21 ,2 claim 21 ,4-oxadiazol-5-yl claim 21 , or 3-cyclopropyl-1 claim 21 ,2 claim 21 ,4-oxadiazol-5-yl.36. The method of claim 21 , wherein W and X taken together with the atoms to which they are bonded form a fused aryl which can be mono- or independently multi-substituted with (C-C)alkyl claim 21 , (C-C)cycloalkyl claim 21 , or halo.37. The method of claim 21 , wherein n is 0 or 1; Ris ethyl claim 21 , 2- ...

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Номер записи: 72
03-07-2014 дата публикации

5-HT2B RECEPTOR ANTAGONISTS

Номер: US20140187585A1
Автор: Thuring Johannes Wilhelmus John F., VER DONCK Luc August Laurentius
Принадлежит: Janssen Pharmaceutica, NV

The present invention relates to novel fluorinated piperidine derivatives having antagonistic activity at the 5-HTreceptor, pharmaceutical compositions comprising these compounds and their use as a medicine. 16.-. (canceled) The present invention relates to novel fluorinated piperidine derivatives having antagonistic activity at the 5-HTreceptor, pharmaceutical compositions comprising these compounds and their use as a medicine.Cisapride is a serotonin 5-HTreceptor agonist useful as a gastroprokinetic drug. It interacts significantly with several other receptors such as 5-HTand 5-HT; D; 5-HT; Alpha, Alpha, Alphaand Alpha. It was withdrawn from some markets in 2000 due to reports of sudden cardiac arrhythmias. At the origin of this side effect is drug-induced QT prolongation by blockade of the hERG potassium channel (human ether-a-go-go related gene). One of the known pharmacophores of a hERG channel blocker comprises a hydrophilic and a hydrophobic moiety linked by a middle part having a basic nitrogen atom. At physiological pH, the basic nitrogen is protonated and is involved in cation-π interaction with Tyr 652 residues within the hERG channel pore. In order to lower the pKa value of piperidine nitrogen atom, and thereby reduce the likelihood of blockade of the hERG channel, derivatives of cisapride were prepared wherein 3-methoxy-piperidine was replaced by 3-fluoropiperidine and 3,3-difluoropiperidine.The present invention concerns a compound of formula (I)or a stereochemically isomeric form thereof, wherein R is hydrogen or fluoro, or an addition salt or a solvate thereofIllustrative of the invention is a pharmaceutical composition comprising a pharmaceutically acceptable carrier and any of the compounds described above. An illustration of the invention is a pharmaceutical composition made by mixing any of the compounds described above and a pharmaceutically acceptable carrier. Illustrating the invention is a process for making a pharmaceutical composition ...

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Номер записи: 73
19-04-2018 дата публикации

PROCESS FOR THE PREPARATION OF LOMITAPIDE

Номер: US20180105487A1
Автор: Mukunda Reddy Jambula, Parthasaradhi Reddy Bandi, Rathnakar Reddy Kura, Vamsi Krishna Bandi
Принадлежит:

The present invention relates to a process for preparing Lomitapide or its pharmaceutically acceptable salt thereof having high purity with acceptable levels of impurities. 16-. (canceled)86. The process as claimed in claim , wherein solvent used in step i) selected from the group comprising of alcohols , halogenated hydrocarbons , polar aprotic solvents , non-polar solvents , wherein alcohols are selected from the group comprising of aliphatic alcohols , aromatic alcohols; halogenated hydrocarbons are selected from the group comprising of chlorinated hydrocarbons; polar aprotic solvents are selected from the group comprising of organic nitriles , amides , ketones , ethereal solvents , esters or mixture thereof.9. The process as claimed in claim 7 , wherein base used in step i) selected from the group comprising of triethyl amine claim 7 , n-butyl lithium claim 7 , sec-butyl lithium claim 7 , sodium hydride claim 7 , potassium hydride claim 7 , sodium hydroxide claim 7 , potassium hydroxide.10. The process as claimed in claim 7 , wherein alkali hydroxide used in step iii) selected from the group comprising of sodium hydroxide claim 7 , potassium hydroxide claim 7 , lithium hydroxide.12. The process as claimed in claim 11 , wherein solvent used in step i) selected from the group comprising of methanol claim 11 , ethanol claim 11 , isopropanol claim 11 , methylene chloride claim 11 , dimethyl formamide claim 11 , ethyl acetate claim 11 , isopropyl acetate claim 11 , acetonitrile claim 11 , heptane claim 11 , toluene claim 11 , n-heptane claim 11 , n-hexane claim 11 , diisopropyl ether claim 11 , tetrahydrofuran claim 11 , 1 claim 11 ,4-dioxane or mixture thereof.13. The process as claimed in claim 11 , wherein debenzylation in step iv) carried out using a metal catalyst is selected from the group comprising of palladium and platinum.14. The process as claimed in claim 11 , wherein acid used in step iv) selected from the group comprising of hydrochloric acid claim 11 , ...

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Номер записи: 74
29-04-2021 дата публикации

COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES

Номер: US20210122713A1
Автор: BERGNER Magnus Gustav Wilhelm, BORGSTRÖM Björn Gustav, Burstein Ethan S., JANSSON Karl Erik, Olsson Roger, SKÖLD Niklas Patrik, VON WACHENFELDT Henrik, WAHLSTRÖM Larisa Yudina
Принадлежит: ACADIA Pharmaceuticals Inc.

The present disclosure relates to compounds according to Formulae (I), (II) and (VIII), useful for treating diseases. 29.-. (canceled)1114.-. (canceled)1617.-. (canceled)19. The compound claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , stereoisomer claim 1 , or deuterated analogue thereof of claim 1 , wherein{'sub': 3', '1-6', '1-6', '2', 's', '3-6', '2', 's', '2-5', '2', 's', '2-5', '2', 's', '5-6, 'Ris selected from the group consisting of hydrogen, deuterium, hydroxyl, —OD, substituted or unsubstituted Calkyl, substituted or unsubstituted Calkoxy, substituted or unsubstituted —(CH)—Ccycloalkyl, substituted or unsubstituted —(CH)—Cheteroalicyclyl, substituted or unsubstituted —(CH)—Cheteroaryl, and substituted or unsubstituted —(CH)—Caryl, wherein each s is selected from the group consisting of 0, 1, 2 and 3; or'}{'sub': 3', '3', '2', '3', '2', '2', '3', '3', '3', '9a', '9b', 't', '9c', '9a', '9b', 't', '9c', '9a', 'w', '9c', '2', 't', '9c', '9a', 'w', '9a', '9b', '2', 't', '9a', '9b', '9a', '9b', '9c', '9d', '9e', '1-4, 'Ris selected from the group consisting of hydrogen, methyl, —CD, ethyl, —CDCD, n-propyl, —CDCDCD, iso-propyl, cyclopropyl, 3-oxetanyl, —CDCDCD, —(CRR)C(═O)OR, —(CRR)(CRR)C(═O)OR, —(CH)(CRR)C(═O)NRRand —(CH)C(═O)NRR, wherein R, R, R, R, and Rindependently are hydrogen or C-alkyl, wherein each of t and w is selected from 0, 1, 2, and 3.'}20. (canceled)21. The compound claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , stereoisomer claim 1 , or deuterated analogue thereof of claim 1 , wherein Ris hydrogen or methyl.23. The compound claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , stereoisomer claim 1 , or deuterated analogue thereof of claim 1 , wherein{'sub': 4a', '4b', '5a', '5b', '3, 'R, R, R, and Rare independently selected from the group consisting of hydrogen, methyl, and —CF; or'}{'sub': 4a', '4b', '5a', '5b, 'R, R, ...

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Номер записи: 75
30-04-2015 дата публикации

Fluorinated Bridged Spiro[2.4]Heptane Derivatives as ALX Receptor Agonists

Номер: US20150118258A1
Автор: Corminboeuf Olivier, Pozzi Davide
Принадлежит:

The present invention relates to fluorinated bridged spiro[2.4]heptane derivatives of formula (I), 2. The compound according to claim 1 , wherein n represents 1; or a salt thereof.3. The compound according to claim 1 , wherein n represents 2; or a salt thereof.4. The compound according to claim 1 , wherein Rrepresents hydrogen; or a salt thereof.5. The compound according to claim 1 , wherein Rrepresents fluoro; or a salt thereof.6. The compound according to claim 1 , wherein Rrepresents hydrogen and the two stereogenic centers at the heterocyclyl group claim 1 , which is attached to the amide nitrogen-atom claim 1 , are relative to each other in trans-configuration; or a salt thereof.7. The compound according to claim 1 , wherein said compound is:(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3S,4S)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3R,4R)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-(cis-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;(1S,2R,3R,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-(3,3-difluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;(1S,2R,3R,4R)—N2-(4-Bromo-2-fluorobenzyl)-N3-(cis-4-fluoropyrrolidin-3-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide; or(1S,2R,3R,4R)—N2-(4-Bromo-2-fluorobenzyl)-N3-(trans-4-fluoropyrrolidin-3-yl)spiro[bicyclo[2.2.1]heptane-7,1′-cyclopropane]-2,3-dicarboxamide;or a salt thereof.8. The compound according to claim 1 , wherein the compound is: (1S claim 1 ,2R claim 1 ,3R claim 1 ,4R)—N2-(4-bromo-2-fluorobenzyl)-N3-((3S claim 1 ,4S)-3-fluoropiperidin-4-yl)spiro[bicyclo[2.2.1]heptane-7 claim 1 ,1′-cyclopropane]-2 claim 1 ,3-dicarboxamide; or a salt thereof.9. The compound according to claim 1 , wherein the compound is: (1S claim 1 ,2R claim 1 ,3R claim 1 ,4R ...

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Номер записи: 76
10-07-2014 дата публикации

PIPERAZINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO

Номер: US20140194422A1
Автор: Ganesh Thota, Lambeth John David, Smith Susane M., Sun Aiming
Принадлежит: EMORY UNIVERSITY

The disclosure relates to piperazine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidase. 2. The pharmaceutical composition of claim 1 , wherein Z is C═O.3. The pharmaceutical composition of claim 1 , wherein Ris alkyl substituted with amino wherein the amino is substituted with an aryl group optionally substituted with one or more alkoxy.4. The pharmaceutical composition of claim 1 , wherein Ris a heterocyclyl optionally substituted with one or more R;5. The pharmaceutical composition of claim 3 , wherein the heterocyclyl is indolyl claim 3 , quinolinyl claim 3 , or imidazolyl.6. A compound of formula I as in claim 1 , selected from the group consisting of2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)-3-methylpiperazin-1-yl)ethanone;2-((4-isopropylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-ethoxyphenyl)piperazin-1-yl)ethanone;2-((3,4-difluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((3-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(3-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(4-fluorophenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-fluorophenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(pyridin-4-yl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone;4-(4-(2-((4-acetylphenyl)amino)acetyl)piperazin-1-yl)benzonitrile;2-((2-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(3,4-dimethoxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl)amino)-1-(4-(2-hydroxyphenyl)piperazin-1-yl)ethanone;2-((4-acetylphenyl) ...

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Номер записи: 77
18-04-2019 дата публикации

HYDROBROMIDE SALT OF N-(4-CHLORO-2-HYDROXY-3-((3S)-3-PIPERIDINYLSULFONYL)PHENYL-N'-(3-FLUORO-2-METHYLPHENYL)UREA

Номер: US20190112269A1
Автор: SANDERSON Francis Dominic, VALLANCE Sarah Mary
Принадлежит:

A compound which is the hydrobromide salt of N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments. 1. A pharmaceutical composition in an oral dosage form comprising a hemihydrate of the hydrobromide salt of N-{4-chloro-2-hydroxy-3-[(3 S)-3-piperidinylsulfonyl]phenyl}-N′-(3-fluoro-2-methylphenyl)urea and one or more pharmaceutically acceptable carriers , diluents or excipients , wherein the oral dosage form is selected from the group consisting of capsule , tablet , powder , granule , solution or suspension in aqueous or non-aqueous liquids , edible foams or whips , oil-in-water liquid emulsion and water-in-oil liquid emulsion.2. The pharmaceutical composition according to claim 1 , wherein the oral dosage form is a tablet or capsule.3. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of ethanol claim 1 , glycerol claim 1 , and water.4. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable carrier is selected from starch and mannitol.5. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable excipient is a lubricant selected from the group consisting of sodium oleate claim 1 , sodium stearate claim 1 , magnesium stearate claim 1 , sodium benzoate claim 1 , sodium acetate claim 1 , and sodium chloride.6. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable excipient is a disintegrator selected from the group consisting of starch claim 1 , methyl cellulose claim 1 , agar claim 1 , bentonite claim 1 , and xanthan gum.7. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable excipient ...

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Номер записи: 78
24-07-2014 дата публикации

(METH)ACRYLATE COMPOUND AND PHOTOCHROMIC CURABLE COMPOSITION CONTAINING THE (METH)ACRYLATE COMPOUND

Номер: US20140203226A1
Автор: Momoda Junji, Takenaka Junji
Принадлежит: TOKUYAMA CORPORATION

A photochromic curable composition that contains a (meth)acrylate compound represented by the following formula (1-X1); 2. The photochromic curable composition according to claim 1 , which contains (A) the (meth)acrylate compound represented by said formula (1) in an amount of 0.01 to 20 parts by mass claim 1 , (B) the radically polymerizable monomer other than the (meth)acrylate compound represented by said formula (1) in an amount of 100 parts by mass claim 1 , and (C) the photochromic compound in an amount of 0.01 to 20 parts by mass.3. The photochromic curable composition according to claim 1 , wherein said photochromic compound (C) contains a compound having an indeno[2 claim 1 ,1-f]naphtho[1 claim 1 ,2-b]pyran skeleton.4. A coating agent containing the photochromic curable composition of .5. An optical material having a photochromic coating obtained by curing the coating agent of on at least one surface of an optical base material.6. A photochromic cured body obtained by curing the photochromic curable composition of . This invention relates to a novel (meth)acrylate compound and to a novel curable composition that contains the (meth)acrylate compound and is useful for the production of optical articles having photochromic property.Photochromic spectacles are the spectacles which, when used outdoors and irradiated with light that includes ultraviolet rays such as sunlight, work as sunglasses with their lenses being quickly colored and, when used indoors and are no longer irradiated with such light, work as ordinary spectacles with their color being faded. In recent years, demands for the photochromic spectacles are increasing.As for the photochromic spectacle lenses, plastic lenses have been specifically preferred from the standpoint light weight and safety. Photochromic properties are, usually, imparted to the plastic lenses by compounding an organic photochromic compound and a polymerizable monomer or the lens together.As the compounding method, there has ...

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Номер записи: 79
12-05-2016 дата публикации

PRODRUGS OF ANTI-PLATELET AGENTS

Номер: US20160130227A1
Автор: Kandula Mahesh
Принадлежит:

The invention relates to the compounds of formula II, formula Ia, formula IIa or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula II, formula Ia, formula IIa and methods for treating or preventing atherothrombosis may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment or management of ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots. 4. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.5. The pharmaceutical composition of claim 4 , wherein said pharmaceutical composition is formulated to treat an underlying etiology with an effective amount administering the patient in need by oral administration claim 4 , delayed release or sustained release claim 4 , transmucosal administration claim 4 , syrup claim 4 , topical administration claim 4 , parenteral administration claim 4 , injection claim 4 , subdermal administration claim 4 , oral solution claim 4 , rectal administration claim 4 , buccal administration or transdermal administration.6. The pharmaceutical composition of claim 5 , wherein the underlying etiology is atherothrombosis claim 5 , ischemia claim 5 , stroke claim 5 , cerebral thrombosis claim 5 , arterial thrombosis claim 5 , thrombotic cerebrovascular claim 5 , cardiovascular diseases and blood clots.7. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.8. The pharmaceutical composition of claim 7 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 7 , delayed release or sustained ...

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Номер записи: 80
11-05-2017 дата публикации

LSD1 Inhibitors

Номер: US20170129857A1
Автор: MARX Matthew Arnold, Vaisburg Arkadii
Принадлежит: Mirati Therapeutics, Inc.

The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention. 2. The compound of claim 1 , wherein X is azetidinyl claim 1 , pyrrolidinyl claim 1 , and piperidinyl claim 1 , wherein each of said azetidinyl claim 1 , pyrrolidinyl claim 1 , and piperidinyl may be optionally independently substituted with one or more C-Calkyl claim 1 , alkoxy claim 1 , halogen or haloalkyl.3. The compound of claim 2 , wherein Y is phenyl claim 2 , indenyl claim 2 , azulenyl claim 2 , naphthyl claim 2 , furanyl claim 2 , thiophenyl claim 2 , 2H-pyrrolo claim 2 , pyrrolo claim 2 , 2-pyrrolinyl claim 2 , 3-pyrrolinyl claim 2 , oxazolyl claim 2 , thiazolyl claim 2 , imidazolyl claim 2 , 2-imidazolinyl claim 2 , pyrazolyl claim 2 , 2-pyrazolinyl claim 2 , isoxazolyl claim 2 , isothiazolyl claim 2 , 1 claim 2 ,2 claim 2 ,3-oxadiazolyl claim 2 , 1 claim 2 ,2 claim 2 ,3-triazolyl claim 2 , 1 claim 2 ,3 claim 2 ,4-thiadiazolyl claim 2 , 2H-pyranyl claim 2 , 4H-pyranyl claim 2 , pyridyl claim 2 , pyridazinyl claim 2 , pyrimidinyl claim 2 , pyrazinyl claim 2 , 1 claim 2 ,3 claim 2 ,5-triazinyl claim 2 , indolininyl claim 2 , indolyl claim 2 , isoindolyl claim 2 , 3H-indolyl claim 2 , indolinyl claim 2 , pyrrolo[2 claim 2 ,3-b]pyridinyl claim 2 , pyrrolo[2 claim 2 ,3-c]pyridinyl claim 2 , pyrrolo[3 claim 2 ,2-c]pyridinyl claim 2 , pyrrolo[3 claim 2 ,2-b]pyridinyl claim 2 , pyrrolo[1 claim 2 ,2-b]pyridiazinyl claim 2 , imidazo[4 claim 2 ,5-b]pyridinyl claim 2 , imidazo[4 claim 2 ,5-c]pyridinyl claim 2 , pyrazolo[4 claim 2 ,3-d]pyridinyl claim 2 , pyrazolo[4 claim 2 ,3-c]pyridinyl claim 2 , pyrazolo[3 claim 2 ,4-b]pyridinyl claim 2 , pyrazolo[3 claim 2 ,4-c]pyridinyl claim 2 , pyrazolo[1 claim 2 ,5-a]pyridinyl claim 2 , imidazo[1 claim 2 ,2-a]pyridinyl claim 2 , imidazo[1 ...

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Номер записи: 81
19-05-2016 дата публикации

HDAC INHIBITORS

Номер: US20160137594A1
Автор: Davidson Alan Hornsby, DAY Francesca Ann, Donald Alastair David Graham, Moffat David Festus Charles
Принадлежит:

Compounds of formula (I) inhibit HDAC activity: 122-. (canceled)24. The compound or pharmaceutically acceptable salt thereof according to wherein the radical HONHC(═O)—W— is attached to the ring containing A claim 23 , B claim 23 , and D in a position meta- or para- to the radical RRCHNHYLX[CH]—.26. The compound or pharmaceutically acceptable salt thereof according to wherein the radical —YLX[CH]— is —CH—.27. The compound or pharmaceutically acceptable salt thereof according to wherein Ris methyl claim 23 , ethyl claim 23 , n- or iso-propyl claim 23 , n- claim 23 , sec- or tert-butyl claim 23 , cyclohexyl claim 23 , allyl claim 23 , phenyl claim 23 , benzyl claim 23 , 2- claim 23 , 3- or 4-pyridylmethyl claim 23 , N-methylpiperidin-4-yl claim 23 , tetrahydrofuran-3-yl or methoxyethyl.28. The compound or pharmaceutically acceptable salt thereof according to wherein Ris cyclopentyl.29. The compound or pharmaceutically acceptable salt thereof according to wherein Ris phenyl claim 23 , benzyl claim 23 , phenylethyl claim 23 , tert-butoxymethyl or iso-butyl.30. The compound or pharmaceutically acceptable salt thereof according to wherein Ris —CH(CH) claim 23 , cyclohexyl claim 23 , —CHO(t-Bu) claim 23 , —CHS(t-Bu) claim 23 , or phenyl.32. The compound or pharmaceutically acceptable salt thereof according to wherein Ris methyl claim 31 , ethyl claim 31 , n- or iso-propyl claim 31 , n- claim 31 , sec- or tert-butyl claim 31 , cyclohexyl claim 31 , allyl claim 31 , phenyl claim 31 , benzyl claim 31 , 2- claim 31 , 3- or 4-pyridylmethyl claim 31 , N-methylpiperidin-4-yl claim 31 , tetrahydrofuran-3-yl or methoxyethyl.33. The compound or pharmaceutically acceptable salt thereof according to wherein Ris cyclopentyl.34. The compound or pharmaceutically acceptable salt thereof according to wherein Ris phenyl claim 31 , benzyl claim 31 , phenylethyl claim 31 , tert-butoxymethyl or iso-butyl.35. The compound or pharmaceutically acceptable salt thereof according to wherein Ris —CH( ...

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Номер записи: 82
09-05-2019 дата публикации

1-ARYLALKYL-4-ACYLAMINOPIPERIDINE COMPOUNDS

Номер: US20190134018A1
Автор: Hruby Victor J., Vardanyan Ruben S.
Принадлежит: Arizona Board of Regents on Behalf of the University of Arizona

The present invention provides a compound of the formula: 2. The method of claim 1 , wherein Ris selected from the group consisting of ethyl claim 1 , 7-bromoheptyl claim 1 , optionally substituted fur-2-yl claim 1 , optionally substituted fur-3-yl claim 1 , optionally substituted thiophen-2-yl claim 1 , optionally substituted thiophen-3-yl claim 1 , and optionally substituted phenyl.3. The method of claim 2 , wherein Ris optionally substituted fur-2-yl claim 2 , optionally substituted fur-3-yl claim 2 , optionally substituted thiophen-2-yl claim 2 , optionally substituted thiophen-3-yl or optionally substituted phenyl.4. The method of claim 1 , wherein Ris C-Calkylene.5. The method of claim 1 , wherein Y is selected from the group consisting of optionally substituted phenyl claim 1 , optionally substituted thiophen-2-yl claim 1 , optionally substituted thiophen-3-yl claim 1 , optionally substituted fur-2-yl claim 1 , optionally substituted fur-3-yl claim 1 , a moiety of the formula —C(═O)—OR claim 1 , where Ris C-Calkyl claim 1 , and a moiety of the formula —C(═O)NRR claim 1 , where each of Rand Ris independently H or C-Calkyl.6. The method of 5 claim 1 , wherein Y is optionally substituted phenyl claim 1 , optionally substituted thiophen-2-yl claim 1 , optionally substituted thiophen-3-yl claim 1 , optionally substituted fur-2-yl or optionally substituted fur-3-yl.9. The method of claim 1 , wherein said clinical condition is opioid overdose or opioid dependency.11. The method of claim 10 , wherein Ris selected from the group consisting of ethyl claim 10 , 7-bromoheptyl claim 10 , optionally substituted fur-2-yl claim 10 , optionally substituted fur-3-yl claim 10 , optionally substituted thiophen-2-yl claim 10 , optionally substituted thiophen-3-yl claim 10 , and optionally substituted phenyl.12. The method of claim 11 , wherein Ris optionally substituted fur-2-yl claim 11 , optionally substituted fur-3-yl claim 11 , optionally substituted thiophen-2-yl claim 11 , ...

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Номер записи: 83
08-09-2022 дата публикации

Method for continuously preparing n,n-bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine

Номер: US20220281840A1
Автор: Baijun YE, Fener Chen, Liangchuan LAI, Meifen JIANG
Принадлежит: FUDAN UNIVERSITY

Disclosed is a method of continuously preparing N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine, which relates to chemical engineering. The Pt/C catalyst and the quartz sand are mixed uniformly and loaded to the continuous-flow fixed-bed reactor. Then, hydrogen gas and a substrate solution containing 2,2,6,6-tetramethyl-4-piperidinone and 1,6-hexanediamine are simultaneously fed to the micro-mixer and the continuous-flow fixed-bed reactor in sequence to undergo a continuous catalytic reductive amination to obtain the N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine.

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Номер записи: 84
09-05-2019 дата публикации

Novel Compounds And Methods For The Treatment Of Alzheimer?s Disease And/Or Cerebral Amyloid Angiopathy

Номер: US20190135832A1
Автор: Boyd Robert
Принадлежит:

Described herein are novel compounds and methods for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA). 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein Ris benzyl.4. The compound of claim 1 , wherein Ris H.5. The compound of claim 1 , wherein Ris benzyl.6. The compound of claim 1 , wherein Ais OR.7. The compound of claim 6 , wherein Ais OH.8. The compound of claim 7 , wherein Ais H.9. The compound of claim 1 , wherein Bis OR.10. The compound of claim 9 , wherein Bis OH.11. The compound of claim 10 , wherein Bis H.12. The compound of claim 1 , wherein Ais OH claim 1 , Ais H claim 1 , Bis OH and Bis H.13. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. the compound of ; and'}b. at least one pharmaceutically acceptable carrier.14. A method for treating Alzheimer's disease and/or cerebral amyloid angiopathy in a patient at risk for developing or diagnosed with the same claim 1 , the method comprising administering to the patient an effective amount of the compound of .15. The method of claim 14 , wherein the administration of an effective amount of the compound increases processing of one or more gangliosides selected from GM2 and GA2.16. The method of claim 14 , wherein the patient is at risk of developing or diagnosed with Alzheimer's disease.17. The method of claim 14 , wherein the patient is at risk of developing or diagnosed with cerebral amyloid angiopathy.18. A method for enhancing the activity of β-hexosaminidase claim 1 , the method comprising administering an effective amount of the compound of .19. A kit comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. the compound of ; and'}b. instructing for using the same to treat Alzheimer's disease and/or cerebral amyloid angiopathy. This is a divisional of U.S. Ser. No. 16/004,723, filed on Jun. 11, 2018, which is a divisional of U.S. Ser. No. 15/ ...

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Номер записи: 85
10-06-2021 дата публикации

AMORPHOUS FORM OF PIMAVANSERIN HEMITARTRATE

Номер: US20210171464A1
Автор: BERTOLOTTI Mattia, Bonanomi Jacopo, Novo Barbara
Принадлежит:

Disclosed is the amorphous form of pimavanserin* hemitartrate, the process for its preparation, and pharmaceutical formulations containing it. 1. Amorphous solid form of pimavanserin hemitartrate.2. The amorphous solid form according to claim 1 , characterised by an IR spectrum comprising absorption peaks at 3361.1 cm claim 1 , 2958.9 cm claim 1 , 1610.7 cm claim 1 , 1508.3 cm claim 1 , 1470.7 cm claim 1 , 1394.8 cm claim 1 , 1219.5 cm claim 1 , 1172.2 cm claim 1 , 1111.2 cm claim 1 , 1030.3 cm claim 1 , 981.0 cm claim 1 , 817.2 cmand 776.5 cm.3. The amorphous solid form according to claim 1 , characterised by the following IR spectrum:4. The amorphous solid form according to claim 1 , characterised by an endothermic peak at 61.49° C. claim 1 , an exothermic peak at 132.79° C. and an endothermic peak at 167.88° C. claim 1 , detected by DSC analysis.5. The amorphous solid form according to claim 1 , characterised by the following DSC curve:6. The amorphous solid form according to claim 1 , characterised by the following XRPD diffractogram:7. A process for preparing the amorphous solid form of pimavanserin hemitartrate according to claim 1 , comprising the steps of:a) dissolving pimavanserin hemitartrate in crystalline form in a suitable polar solvent at a temperature ranging between 16° C. and 100° C.;b) rapidly cooling the solution to a temperature ranging between −50° C. and 0° C.;c) keeping the solution under vacuum at a temperature ranging between −50° C. and 0° C. for a time of between 0 and 72 hours;d) recovering the resulting solid.8. A process for preparing the amorphous solid form of pimavanserin hemitartrate according to claim 1 , comprising the steps of:a) dissolving pimavanserin hemitartrate in crystalline form in a suitable polar solvent at a temperature ranging between 16° C. and 100° C.;b) evaporating the solvent on a thin layer at a temperature ranging between −20° C. and 120° C. at atmospheric pressure until the solvent has completely evaporated;c) ...

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Номер записи: 86
14-08-2014 дата публикации

FENTANYL DERIVATIVES AS PH-DEPENDENT OPIOID RECEPTOR AGONISTS

Номер: US20140228406A1
Автор: Scharkoi Olga, Stein Christoph, Weber Marcus, Zöllner Christian
Принадлежит:

The invention relates to fluorinated fentanyl derivatives that function as opioid receptor agonists, which activate target opioid receptors in a pH-dependent manner, and are thus selective for the receptors in inflamed (acidic) milieu; uses thereof and pharmaceutical compositions comprising them. 3. Compound according to claim 1 , wherein said compound is an opioid receptor agonist that activates a target opioid receptor in a pH-dependent manner.4. Compound according to claim 1 , wherein activation of said receptor by the compound occurs selectively a pH value below 7.5. Compound according to claim 1 , wherein said compound exhibits a pKa value between 4 and 7.6. Compound according to claim 1 , wherein said compound comprises a protonated N-group.7. Compound according to claim 1 , wherein said target opioid receptor is selected from the group consisting of the mu-receptor claim 1 , delta-receptor and kappa-receptor.8. Compound according to claim 1 , wherein the compound activates the target opioid receptor in conditions of inflammation-associated pH in inflamed tissue.9. Compound according to claim 1 , wherein the compound binds and activates opioid receptors at the terminals of peripheral sensory neurons.10. Compound according to claim 1 , wherein the compound exhibits inflammation-specific peripheral analgesic function in inflamed or injured tissues without causing central or intestinal effects.11. (canceled)12. A method of treating inflammation-associated pain comprising administering to a subject a compound according to .13. Pharmaceutical composition comprising the compound according to claim 1 , and/or a salt claim 1 , derivative and/or stereoisomer thereof claim 1 , together with at least one pharmaceutically acceptable carrier.14. Pharmaceutical composition according to claim 13 , comprising a mixture of at least 2 compounds according to formulae II claim 13 , III claim 13 , IV and/or V claim 13 , and/or salts claim 13 , derivatives and/or stereoisomers ...

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Номер записи: 87
18-06-2015 дата публикации

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

Номер: US20150166481A1
Автор: MORI Kohei, NISHIYAMA Akira, NOJIRI Masutoshi, TAOKA Naoaki
Принадлежит: KANEKA CORPORATION

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing. 121-. (canceled) The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate, and to intermediates useful for producing the 3-aminopiperidine.As methods for producing an optically active 3-aminopiperidine or salt thereof, or a derivative of optically active 3-aminopiperidine, for example, the following methods are known:1) a method, wherein L-ornithine monohydrochloride is methyl-esterified, and then (S)-3-amino piperidone is obtained by chromatography with an ion exchange resin, the (S)-3-amino piperidone is reacted with lithium aluminum hydride to be (S)-3-aminopiperidine, an inorganic salt is removed by filtration, and the target compound is purified (Non-patent Document 1);2) a method, wherein ethyl nipecotate is optically resolved using L-tartaric acid, the nitrogen atom is protected with benzyloxycarbonyl group, the ethyl ester is hydrolyzed in alkaline condition, Curtius rearrangement is carried out using ...

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Номер записи: 88
18-06-2015 дата публикации

Derivatives of 1-phenoxy propan-2-ol and pharmaceutical composition containing the same

Номер: US20150166496A1
Автор: Changjoon Justin LEE, Dong Ho WOO, Dong-Gyu Kim, Eun Mi Hwang, Eun-Joo Roh, Hee-jung Chun, Jeong Eun Yang, Jung-Eun Park, Kye-Jung Shin, Soo Jin Oh, Soon-Hyouk Lee, Wan-Keun Ji, Yun-Soo Na
Принадлежит: Korea Advanced Institute of Science and Technology KAIST

The present invention relates to a novel phenoxypropanol derivative, use thereof for blocking T-type calcium channel and/or TREK channel, and use thereof for preventing and/or treating T-type calcium channel- and/or TREK channel-associated diseases.

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Номер записи: 89
15-06-2017 дата публикации

Compounds And Methods For The Treatment Of Alzheimer's Disease And/Or Cerebral Amyloid Angiopathy

Номер: US20170166588A1
Автор: Boyd Robert
Принадлежит:

Described herein are novel compounds and methods for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA). 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein Ris benzyl.6. The compound of claim 5 , wherein Ris H.7. The compound of claim 5 , wherein Ris benzyl.10. The compound of claim 9 , wherein Ris H.11. The compound of claim 9 , wherein Ris benzyl.13. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. the compound of ; and'}b. at least one pharmaceutically acceptable carrier.14. A method for preventing and/or treating Alzheimer's disease and/or cerebral amyloid angiopathy in a patient at risk for developing or diagnosed with the same claim 1 , the method comprising administering to the patient an effective amount of the compound of .15. The method of claim 14 , wherein the administration of an effective amount of the compound increases processing of one or more gangliosides selected from GM2 and GA2.16. A method for enhancing the activity of β-hexosaminidase claim 1 , the method comprising administering an effective amount of the compound of .17. A kit comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. the compound of ; and'}b. instructing for using the same to treat and/or prevent Alzheimer's disease and/or cerebral amyloid angiopathy. This application claims the benefit under 35 U.S.C. §119(e) to U.S. Provisional Application No. 62/266,760, filed Dec. 14, 2015, the entire contents of which are incorporated herein by reference in their entirety.The present invention generally pertains to the treatment of human cerebral amyloidoses such as Alzheimer's disease and/or cerebral amyloid angiopathy.Alzheimer's disease is one of the largest socioeconomic healthcare burdens. Alzheimer's disease is characterized by progressive dementia and histopathologically by the presence of neurofibrillary tangles (NFTs) ...

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Номер записи: 90
21-05-2020 дата публикации

(2E,4E)-5-PHENYL-PENTA-2,4-DIEN-1-ONE DERIVATIVE

Номер: US20200157048A1
Автор: JOSHI Dirgha Raj, Kim Hak Sung, Kim Jong Woo, KWON Sang Hoon, LEE Chi Woo
Принадлежит:

The present application relates to a novel pentadienoyl compound and a pharmaceutical composition including the same. The pentadienoyl compound of the present application may be used to prevent or treat fatty liver and fatty liver-related disease by inhibiting lipogenesis and lipid accumulation in cells and activating lipid metabolism. In addition, the pentadienoyl compound of the present application may increase a SIRT1 expression level in cells or SIRT1 activity, and thus may be used to prevent or treat a SIRT1-mediated disease. In addition, the pentadienoyl compound of the present application may reduce a CK2 expression level in cells or CK2 activity, and thus may be used to prevent or treat a CK2-mediated disease. 2. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare independently selected from H claim 1 , —OR claim 1 , and —SR;{'sub': 11', '1', '6, 'each Ris independently unsubstituted or substituted C-Calkyl, wherein the alkyl is linear alkyl, branched alkyl, or cycloalkyl;'}{'sub': 3', '4', '6', '6', '3', '2', '4', '2, 'Xand Xare CRR′, wherein, when Xis CH, Xis not CH;'}{'sub': 6', '6', '31', '31', '31', '3', '2', '31', '31', '2', '31', '31', '2', '31', '31', '2', '31, 'each Rand R′ are independently selected from H, a halogen, R, —OH, —OR, —SH, —SR, —CN, —N, —NH, —NHR, —N(R), —C(═O)H, —C(═O)R, —C(═O)OH, —C(═O)OR, —C(═O)NH, —C(═O)NHR, —C(═O)N(R), —NHC(═O)H, —NHC(═O)OH, and —NHC(═O)R;'}{'sub': 6', '6, 'both Rand R′ are not H at once; and'}{'sub': 31', '1', '6, 'each Ris independently unsubstituted or substituted C-Calkyl, wherein the alkyl is linear alkyl, branched alkyl, or cycloalkyl.'}3. The compound of or pharmaceutically acceptable salt thereof claim 2 , wherein Ris selected from —OH claim 2 , —OR claim 2 , —NH claim 2 , and —N claim 2 , and R′ is H.4. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare independently selected from H claim 1 , —OR claim 1 , and —SR;{'sub': 11', '1', ' ...

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Номер записи: 91
01-07-2021 дата публикации

Orally Active Melanocortin Receptor-4 Compounds

Номер: US20210198201A1
Автор: Axel Metzger, James Bullington, John Harold Dodd
Принадлежит: Palatin Technologies Inc

A compound of the formula where R 1 , R 2 , R 3 , R 4 , R 5 , R 6a , and R 6b are as defined in the specification and claims, or an enantiomer, stereoisomer or diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, and the use thereof in the treatment of diseases, disorders, syndromes and conditions responsive to modulation of a melanocortin receptor.

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Номер записи: 92
22-06-2017 дата публикации

POTENT SOLUBLE EPOXIDE HYDROLASE INHIBITORS

Номер: US20170174665A1
Автор: Hammock Bruce D., Inceoglu Ahmet Bora, Lee Kin Sing Stephen
Принадлежит:

The invention discloses a new series of inhibitors of soluble epoxide hydrolase (sEH) with improved physical properties that enhance their druglikeness to treat sEH associated diseases such as chronic diabetic neuropathic pain. 3. The compound of claim 2 , wherein the compound is selected from the group consisting of: 1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-isobutyrylpiperidin-4-yl)urea (Compound 19); 1-(1-(tetrahydro-2H-pyran-4-carbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (Compound 1); 1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-3-(3-fluoro-4-(trifluoromethoxy)phenyl)urea (Compound 24); (5)-1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-(2-methylbutanoyl)piperidin-4-yl)urea (Compound 26); and 1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-(tetrahydro-2H-pyran-4-carbonyl)piperidin-4-yl)urea (Compound 29).4. The compound of claim 3 , wherein the compound is 1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-isobutyrylpiperidin-4-yl)urea (Compound 19).5. The compound of claim 3 , wherein the compound is 1-(1-(tetrahydro-2H-pyran-4-carbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (Compound 1).6. The compound of claim 3 , wherein the compound is 1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-3-(3-fluoro-4-(trifluoromethoxy)phenyl)urea (Compound 24).7. The compound of claim 3 , wherein the compound is (S)-1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-(2-methylbutanoyl)piperidin-4-yl)urea (Compound 26).8. The compound of claim 3 , wherein the compound is 1-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(1-(tetrahydro-2H-pyran-4-carbonyl)piperidin-4-yl)urea (Compound 29).9. A method for increasing the water solubility of a compound of comprising incorporating a heteroatom at X.10. The method of claim 9 , wherein the heteroatom is nitrogen or oxygen.11. A method for increasing water solubility of the compound of comprising incorporating one or more heterocycles at R7.12. A method for decreasing melting point of the compound of comprising incorporating a fluorine at ...

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Номер записи: 93
28-05-2020 дата публикации

METHODS FOR PREPARING N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND POLYMORPHIC FORM

Номер: US20200165202A1
Автор: Boudier Andreas Philipp, Carlos Marlon, Fleming Matthew J., Hillgren Mikael, Olsson Roger, Tandel Sagun, Weber Beat T.
Принадлежит: ACADIA Pharmaceuticals Inc.

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N,-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —OR, or —NRR; Ris hydrogen or substituted or unsubstituted heteroalicyclyl, Ris substituted or unsubstituted aralkyl; X is —ORor —NRR; (wherein Ris hydrogen or substituted or unsubstituted Calkyl and one of Rand Ris hydrogen and the other is hydrogen or N- methylpiperidin-4-yl); and Ris —OCHCH(CH)or F; Also disclosed herein is the tartrate salt of N-(4-fluorobemzyl)-N-(1-methylpiperidin-4-yl)-N′,-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt. 211. (canceled)12. The method according to claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , butyl claim 1 , pentyl claim 1 , trifluoroethyl and phenyl.13. The method according to claim 12 , wherein Ris phenyl.1416-. (canceled)17. The method according to claim 1 , wherein the intermediate according to Formula (A2) is phenyl (4-isobutoxybenzyl)carbamate.18. The method according to any one of claim 1 , further comprising:(c) contacting the pimavanserin produced from step (b) with (L)-tartaric acid to produce a pimavanserin tartrate salt.19. The method according to claim 18 , wherein the pimavanserin tartrate salt is a hemi-tartrate salt.20. The method according to claim 18 , wherein in step (c) claim 18 , the pimavanserin produced from step (b) is contacted with (L)-tartaric acid in methyl ethyl ketone to produce a pimavanserin tartrate salt obtained as a polymorphic Form C characterized by having an endotherm with an onset of between 167 and 177° C. as obtained by differential scanning calorimetry (DSC).21. The method according to claim 20 , wherein the DSC shows no peak between 120 and ...

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Номер записи: 94
29-06-2017 дата публикации

NOVEL COMPOUNDS AS ANTI-TUBERCULAR AGENTS

Номер: US20170183305A1
Автор: DUGAR Sundeep, Mahajan Dinesh, Rai Santosh Kumar, RAO Kanury, SINGH Varshneya
Принадлежит:

The present invention relates to novel compounds of formula (1): The present invention also discloses compounds of formula (1) along with other pharmaceutical acceptable excipients and use of the compounds as anti-tubercular agents. 3. A compound of Formula (1) , including its salts , hydrates and stereoisomers thereof wherein said compound is selected from the group comprising:i. 1-Methylpiperidin-3-yl-2-hydroxy-2,2-diphenylacetate;ii. 3-(2-Hydroxy-2,2-diphenylacetoxy)-1-(((isopropylcarbamoyl)oxy)methyl)-1-methylpiperidin-1-ium;iii. Piperidin-3-yl 2-hydroxy-2,2-diphenylacetate;iv. 1-Benzylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;v. 1-(Methylsulfonyl)piperidin-3-yl 2-hydroxy-2,2-diphenylacetate;vi. 1-(Dimethylcarbamoyl) piperidin-3-yl 2-hydroxy-2,2-diphenylacetate;vii. 1-Benzylpiperidin-4-yl 2-hydroxy-2,2-diphenylacetate;viii. 3-(2-Hydroxy-2,2-diphenylacetoxy)-1-methylquinuclidin-1-ium;ix. 1-Benzylpyrrolidin-3-yl 2-hydroxy-2,2-diphenylacetate;x. 1-Ethylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xi. 1-(Isopropylcarbamoyl) piperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xii. 1-Propylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xiii. 1-Methylpiperidin-4-yl 2-hydroxy-2,2-diphenylacetate;xiv. 1-Benzylazetidin-3-yl 2-hydroxy-2,2-diphenylacetate;xv. 1-Acetylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xvi. 2-Hydroxy-2,2-diphenyl-N-(piperidin-3-yl)acetamide;xvii. N-(1-Benzylpiperidin-4-yl)-2-hydroxy-2,2-diphenylacetamide;xviii. 1-Methylpyrrolidin-3-yl 2-hydroxy-2,2-diphenylacetate;xix. Quinuclidin-3-yl 2-hydroxy-2,2-diphenylacetate;xx. 2-Hydroxy-N-(1-methylpiperidin-3-yl)-2,2-diphenylacetamide;xxi. N-(1-Benzylpiperidin-4-yl)-2-hydroxy-2,2-diphenylacetamide;xxii. N-(1-Benzylazetidin-3-yl)-2-hydroxy-2,2-diphenylacetamide;xxiii. Azetidin-3-yl 2-hydroxy-2,2-diphenylacetate;xxiv. (S)-1-Benzylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xxv. (R)-1-Benzylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xxvi. (S)-1-Methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate;xxvii. (R)-1- ...

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Номер записи: 95
29-06-2017 дата публикации

METHOD FOR PRODUCING SYNTHETIC PENTAPEPTIDE

Номер: US20170183307A1
Автор: Kano Takaaki, MURAYAMA Asami
Принадлежит: MARUISHI PHARMACEUTICAL CO., LTD.

Provided are a method for industrially advantageously producing a highly purified pentapeptide and an intermediate thereof. 2. The compound or a salt thereof according to claim 1 , wherein Ris an alkyl group.3. The compound or a salt thereof according to claim 1 , wherein the compound or a salt thereof is an acid addition salt of the compound.5. The compound or a salt thereof according to claim 1 , wherein Ris an aralkyl group.6. The compound or a salt thereof according to claim 1 , wherein Ris a linear alkyl group having 1 to 12 carbon atoms.7. The compound or a salt thereof according to claim 1 , wherein Ris a branched alkyl group having 1 to 12 carbon atoms.8. The compound or a salt thereof according to claim 1 , wherein Ris a linear alkyl group having 1 to 8 carbon atoms.9. The compound or a salt thereof according to claim 1 , wherein Ris a branched alkyl group having 1 to 8 carbon atoms.10. The compound or a salt thereof according to claim 1 , wherein Ris a linear alkyl group having 1 to 4 carbon atoms.11. The compound or a salt thereof according to claim 1 , wherein Ris a branched alkyl group having 1 to 4 carbon atoms.12. The compound or a salt thereof according to claim 1 , wherein Ris an alkyl group selected from the group consisting of methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl and tert-butyl.13. The compound or a salt thereof according to claim 1 , wherein Ris methyl.14. The compound or a salt thereof according to claim 1 , wherein Ris an aralkyl group having 7 to 18 carbon atoms.15. The compound or a salt thereof according to claim 1 , wherein Ris an aralkyl group that is a Caryl-Calkyl group.16. The compound or a salt thereof according to claim 1 , wherein Ris an aralkyl group that is a phenyl-Calkyl group.17. The compound or a salt thereof according to claim 1 , wherein Ris a benzyl group.18. The compound or salt thereof according to claim 3 , which is an acid addition salt selected from the group consisting of a ...

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Номер записи: 96
18-09-2014 дата публикации

PROCESSES AND INTERMEDIATES FOR PREPARING A MEDICAMENT

Номер: US20140275126A1
Автор: Ben Haim Cyril, Conza Matteo, Houpis Ioannis Nicolaos, Pye Philip
Принадлежит:

Disclosed is a process for the preparation of the following compounds: 5. A process as claimed in claim 3 , wherein the reaction is with (ii) a formamidine salt in which the counterion is a halide or oxygen-based anion.6. A process as claimed in any one of claim 3 , wherein the reaction is performed at a temperature of below 160° C. claim 3 , for instance between 100° C. and 140° C.7. A compound of formula (III) claim 3 , characterised in that it has an ee of greater than 50%.8. A compound of formula (I) claim 1 , (II) or (IVA) (or derivatives thereof) as defined in .10. A use of a compound of formula (I) claim 1 , (IVA) claim 1 , (IV) and/or (III) (or derivatives thereof) as defined in as intermediates in the preparation of ibrutinib.11. A process for the preparation of a pharmaceutical formulation comprising ibrutinib claim 9 , which process comprises bringing into association ibrutinib (or a pharmaceutically acceptable salt thereof) claim 9 , which is prepared as claimed in claim 9 , with (a) pharmaceutically acceptable excipient(s) claim 9 , adjuvant(s) claim 9 , diluents(s) and/or carrier(s). The present invention relates to synthesis procedures and synthesis intermediates of substituted bicyclic compounds, especially compounds that are useful as medicaments, for instance Bruton's tyrosine kinase (Btk) inhibitors such as ibrutinib.Ibrutinib is an organic small molecule having IUPAC name 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one. It is described in a number of published documents, including international patent application WO 2008/039218 (Example 1b), and is described as an irreversible inhibitor of Btk.Btk plays an essential role in the B-cell signaling pathway linking cell surface B-cell receptor stimulation to downstream intracellular responses. Btk is a key regulator of B-cell development, activation, signaling, and survival (Kurosaki, 2000, 276-281; Schaeffer and Schwartzberg, 2000, 282-288). In ...

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Номер записи: 97
15-07-2021 дата публикации

SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Номер: US20210214375A1
Автор: Buzard Daniel J., GRICE Cheryl A., SHAGHAFI Michael B., WEBER Olivia D.
Принадлежит:

Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —Ccycloalkyl-COH.4. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C≡C—Calkyl-COH.6. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is —CH—.7. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is —C(O)—.16. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.17. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.18. The compound of of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both H.19. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from halogen and Chaloalkyl.20. The compound of any one of - claim 1 , or a solvate ...

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Номер записи: 98
06-07-2017 дата публикации

Sugar Derivatives Comprising Sulfur-Containing Moieties And Methods Of Making Same And Methods Of Using The Same For The Treatment Of MPS IIIC

Номер: US20170190665A1
Автор: Boyd Robert, LEE GARY
Принадлежит:

Described herein are modified sugar, iminosugar and azasugar compounds and methods of making same. One or more of these modified compounds contain sulfates, sulfites, sulfamates and/or sulfonamides. Also described are pharmaceutical compositions/formulations comprising these compounds, as well as methods using these modified sugar compounds for the treatment of MPS IIIC (also known as Sanfilippo Type C). 7. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. the compound of ; and'}b. at least one pharmaceutically acceptable carrier.8. A method of making a pharmaceutical composition according to , the method comprising , adding to at least one pharmaceutically acceptable carrier to the compound of .9. A method of making the compound according to claim 4 , the method comprising reacting N-benzyl(N-acetyl 1 claim 4 ,2 deoxynojiimycin) with SOCland pyridine.10. A method of making the compound having a structure represented by formula (V) according to claim 6 , the method comprisinga. reacting 1-deoxygalactonojirimycin with EtOCOCl to produce an intermediate; and{'sub': '2', 'b. reacting the intermediate with SOCl and pyridine.'}11. A method of making the compound having a structure represented by formula (VI) according to claim 6 , the method comprisinga. reacting 1-deoxygalactonojirimycin with EtOCOCl to produce an intermediate; and{'sub': 2', '2, 'b. reacting the intermediate with SOCland pyridine.'}12. A method of making the compound having a structure represented by formula (VII) according to claim 6 , the method comprisinga. reacting 1-deoxynojirimycin with EtOCOCl to produce an intermediate; and{'sub': 2', '2, 'b. reacting the intermediate with SOCland pyridine.'}17. A method of preventing and/or treating MPS IIIC claim 1 , the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of .18. The method of claim 17 , further comprising administering an effective amount ...

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Номер записи: 99
11-06-2020 дата публикации

METHODS FOR PREPARING N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND POLYMORPHIC FORM

Номер: US20200181087A1
Автор: Boudier Andreas Philipp, Carlos Marlon, Fleming Matthew J., Hillgren Mikael, Olsson Roger, Tandel Sagun, Weber Beat T.
Принадлежит: ACADIA Pharmaceuticals Inc.

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —ORor —NRR; Ris hydrogen or substituted or unsubstituted heteroalicyclyl, Ris substituted or unsubstituted aralkyl; X is —ORor —NRR; (wherein Ris hydrogen or substituted or unsubstituted Calkyl and one of Rand Ris hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and Ris —OCHCH(CH)or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt. 224-. (canceled)25. The method according to claim 1 , wherein Ris 4-isobutoxybenzyl.27. The method according to claim 26 , wherein Y is a substituted or unsubstituted imidazolyl.28. The method according to claim 27 , wherein Y is an unsubstituted imidazolyl.30. The method according to claim 29 , wherein the produced intermediate according to Formula (A2) is isolated prior to being contacted by the intermediate according Formula (B2).31. The method according to claim 29 , wherein the (4-isobutoxyphenyl)methanamine is contacted by carbonyldiimidazole to produce the intermediate according to Formula (A2) claim 29 , which is subsequently contacted by the intermediate according to Formula (B2) in a telescoping synthesis.32. The method according to claim 1 , further comprising contacting the pimavanserin produced from the previous step with (L)-tartaric acid to produce a pimavanserin tartrate salt.33. The method according to claim 32 , wherein the pimavanserin tartrate salt is a hemi-tartrate salt.34. The method according to claim 32 , wherein the produced pimavanserin is contacted with (L)-tartaric in methyl ethyl ketone to produce a pimavanserin tartrate ...

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