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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 4703. Отображено 100.
03-05-2012 дата публикации

Processes for preparing amine salts of sildenafil-analogues and use thereof

Номер: US20120108604A1
Автор: Ing-Jun Chen
Принадлежит: KAOHSIUNG MEDICAL UNIVERSITY

A series of amine salts including a structure of formula (I) and formula (III) have provided. In formula I or formula (III), R 1 , R a and RX are as defined in the specification. The amine complex salts disclosed in the present invention are characterized in a pro-drug active form and various pharmaceutical function.

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Номер записи: 1
03-01-2013 дата публикации

Method for the detection of prediabetes

Номер: US20130004972A1
Автор: Toshiaki Watanabe
Принадлежит: Fukuoka University

Provided is a method for prediabetes screening by means of methylglyoxal-modified arginine derivative assay, with which it is possible to treat many samples as simply and as safely as with blood sugar assay, and to collect a blood sample taken during a primary health screening in one procedure without imposing any time restraints, complications or risks on the subject. The method for prediabetes screening by means of methylglyoxal-modified arginine derivative assay comprises assaying the methylglyoxal-modified arginine derivative in blood using an assay system which employs an antibody that specifically recognizes methylglyoxal-modified arginine derivative.

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Номер записи: 2
14-03-2013 дата публикации

PHARMACEUTICAL COMPOUNDS

Номер: US20130065900A1
Автор: Boyce Richard Justin, Boyle Robert George, Walker David Winter
Принадлежит: SENTINEL ONCOLOGY LIMITED

The invention provides a compound of the formula (1): 3. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein Ar is selected from optionally substituted phenyl and optionally substituted five and six membered heteroaryl groups containing one claim 1 , two or three heteroatom ring members selected from O claim 1 , N and S.4. A compound according to claim 3 , or a salt claim 3 , N-oxide or tautomer thereof claim 3 , wherein Ar is optionally substituted phenyl.5. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein each Ris independently selected from a group Rconsisting of halogen; cyano; nitro; a monocyclic carbocyclic or heterocyclic group having from 3 to 10 ring members claim 1 , of which 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 or 4 are heteroatom ring members selected from O claim 1 , N and S and oxidised forms thereof claim 1 , the carbocyclic or heterocyclic group being and optionally substituted with one or more substituents R; or{'sup': a1', 'b1, 'a group R—R;'}{'sup': a1', '1a', '2a', '2a', '1a', '1a', '2a', '1a', 'c1', 'c1', 'c1, 'sub': 2', '2', '2, 'Ris a bond, O, CO, XC(X), C(X)X, XC(X)X, S, SO, SO, NR, SONRor NRSO;'}{'sup': 'b1', 'claim-text': hydrogen;', {'sup': '14a', 'a carbocyclic and heterocyclic group having from 3 to 10 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S and oxidised forms thereof, the carbocyclic or heterocyclic group being optionally substituted with one or more substituents R;'}, {'sub': 1-8', '1-8', '1-8', '2, 'sup': 14a', 'c1', '1a', '2a', '2a', '1a', '1a', '2a', '1a, 'an acyclic Chydrocarbyl group optionally substituted with one or more substituents selected from hydroxy; oxo; halogen; cyano; nitro; carboxy; amino; mono- or di-Cnon-aromatic hydrocarbylamino; and monocyclic carbocyclic and heterocyclic groups having from 3 to 10 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members ...

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Номер записи: 3
28-03-2013 дата публикации

REGIOSELECTIVE PREPARATION OF SUBSTITUTED PYRIMIDINES

Номер: US20130079519A1
Автор: DURAN Adil, GOEPPER Stefan, HALMER Joerg, Konrad Michael
Принадлежит:

The present invention relates to a method of making pyrimidines of formula (III) wherein X1, X2, R1 and R2 have the meanings as defined herein. 2. The method of wherein X1 and X2 are the same or different leaving groups independently selected from halide claim 1 , arylsulfonate claim 1 , alkylsulfonate claim 1 , perfluoroalkylsulfonate claim 1 , arylsulfinate and alkylsulfinate.3. The method of wherein X1 and X2 are the same or different leaving groups and are each independently halides.4. The method of wherein X1 and X2 are chloride.5. The method of wherein one of R1 and R2 is hydrogen and the other is an aromatic group claim 1 , such as e.g. optionally substituted phenyl.6. The method of wherein said non-nucleophilic auxiliary base is N claim 1 ,N-diisopropyl-ethylamine.7. The method of wherein said non-nucleophilic alcohols are tert-butanol claim 1 , tert-pentanol claim 1 , neo-pentanol claim 1 , sec-pentanol and sec-isoamylalcohol.8. The method of wherein said reaction is conducted in tert-butanol as reaction solvent.9. The method of wherein said reaction is conducted at a reaction temperature from about room temperature to about boiling temperature of the solvent(s) used.10. The method of wherein said reaction is conducted at a reaction temperature from about 40° C. to about 80° C.11. The method of wherein said reaction is conducted at about 80° C.12. The method of characterized in that said reaction is conducted without any Lewis acidic metal cation.13. The method of further comprising the steps of precipitating the compound of formula III from the reaction mixture claim 1 , collecting the precipitate claim 1 , washing the precipitate and drying the precipitate.14. The method of further comprising the step of reacting said compound of formula III with an oxygen claim 1 , sulphur or nitrogen nucleophile.15. The method of further comprising suspending the precipitate in water after it is precipitated from the reaction mixture.16. The method of characterized in ...

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Номер записи: 4
18-04-2013 дата публикации

NOVEL THIOUREA OR UREA DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING AIDS, CONTAINING SAME AS ACTIVE INGREDIENT

Номер: US20130096138A1
Автор: Chung Koo Hwan, Han Gyoon Hee, Lee Chul Ho, Song Doo Na, You Ji Chang
Принадлежит: AVIXGEN INC.

Disclosed are novel thiourea or urea derivatives inhibitory of HIV activity. Also provided are a method for preparing the thiourea or urea derivatives, and a pharmaceutical composition for the prophylaxis or therapy of AIDS comprising the derivatives. Having high inhibitory activity against HIV, the thiourea or urea derivatives can be effectively used in the prophylaxis or therapy of AIDS. 3. The thiourea or urea derivative claim 1 , or the pharmaceutically acceptable salt of claim 1 , wherein the thiourea or urea derivative is selected from the group consisting of:1-(4-tert-butyl-benzoyl)-3-(5-hydroxy-naphthalen-1-yl)-thiourea1-(4-tert-butyl-benzoyl)-3-(3-dimethylamino-propyl)-thiourea,1-(4-tert-butyl-benzoyl)-3-(3-dimethylamino-2,2-dimethyl-propyl)-thiourea,4-tert-butyl-N-(4-ethyl-piperazin-1-carbothioyl)-benzoamide,3-(4-tert-butyl-benzoyl)-1-(2-diethylamino-ethyl)-1-methyl-thiourea,3-(4-tert-butyl-benzoyl)-1-(2-dimethylamino-ethyl)-1-methyl-thiourea,1-(4-tert-butyl-benzoyl)-3-(4-diethylamino-1-methyl-butyl)-thiourea,1-(4-tert-butyl-benzoyl)-3-(4-methyl-benzyl)-thiourea,1-(4-tert-butyl-benzoyl)-3-(2-methyl-benzyl)-thiourea,1(4 tert-butyl-benzoyl)-3-(3-propylamino-propyl)-thiourea,1(4 tert-butyl-benzoyl)-3-phenethyl-thiourea,1-(4-tert-butyl-benzoyl)-3-(4-chloro-benzyl)-thiourea,1-(4-tert-butyl-benzoyl)-3-(3-chloro-benzyl)-thiourea,1-(4-tert-butyl-benzoyl)-3-(naphthalen-2-ylmethyl)-thiourea,4-tert-butyl-N-[4-(4-fluoro-phenyl)-piperazin-1-carbothioyl]-benzamide,1-(4-tert-butyl-benzoyl)-3-cyclohexyl-thiourea,1-(4-tert-butyl-benzoyl)-3-(2-fluoro-benzyl)-thiourea,1-benzoyl-3-(naphthalen-2-ylmethyl)-thiourea,1-benzoyl-3-[2-(4-chloro-phenyl)-ethyl]-thiourea,1-benzoyl-3-(4-diethylamino-1-methyl-butyl)-thiourea,3-benzoyl-1-(2-diethylamino-ethyl)-1-methyl-thiourea,N-(4-ethyl-piperazin-1-carbothioyl)-4-methyl-benzamide,1-cyclohexyl-3-(4-methyl-benzoyl)-thiourea,1-(4-chloro-benzyl)-3-(4-methyl-benzoyl)-thiourea,1-(3-dimethylamino-propyl)-3-(4-methyl-benzoyl)-thiourea,1-(4- ...

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Номер записи: 5
25-04-2013 дата публикации

METHOD OF TREATING DIABETES, METABOLIC SYNDROME AND OBESITY USING PHENYLACETAMIDE DERIVATIVE

Номер: US20130102617A1
Автор: Amino Nobuaki, Hayakawa Masahiko, Kanai Akira, Kido Yoshiyuki, Maki Keisuke, Nigawara Takahiro, Okumura Mitsuaki
Принадлежит: Astellas Pharma Inc.

Phenylacetamide compounds of the formula 1. (canceled)2. The method of claim 18 , wherein n is 0.3. The method of claim 2 , wherein Ris methyl claim 2 , trifluoromethyl claim 2 , or cyclopropyl.4. The method of claim 3 , wherein Ris cyclopropyl.6. The method of claim 5 , wherein Ring A is pyrazolyl claim 5 , thiazolyl claim 5 , thiadiazolyl claim 5 , pyridyl or pyrazinyl claim 5 , each of which may be substituted with up to five moieties independently selected from the group consisting of halogen claim 5 , cyano claim 5 , lower alkyl which may be substituted with —OR claim 5 , —OR claim 5 , —O-lower alkylene —OR claim 5 , and —C(O)R.7. The method of claim 6 , wherein [Chem. 21] is a single bond.8. The method of claim 6 , wherein [Chem. 22] is a double bond.9. The method of claim 18 , wherein the compound is selected from the group consisting of:(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-fluoro-1,3-thiazol-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2R)—N-(4-acetyl-1,3-thiazol-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyridin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)—N-(5-chloropyrazin-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methoxypyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-hydroxycyclopentyl]-N-(5 ...

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Номер записи: 6
02-05-2013 дата публикации

2-(2-FLUORO-SUBSTITUTED PHENYL)-6-AMINO-5-CHLORO-4-PYRIMIDINECARBOXYLATES AND THEIR USE AS HERBICIDES

Номер: US20130109573A1
Автор: Epp Jeffrey B., Lo William C., Schmitzer Paul R., Yerkes Carla N.
Принадлежит: DOW AGROSCIENCES LLC

2-(2-Fluoro-substituted phenyl)-6-amino-5-chloro-4-pyrimidine carboxylic acid and its derivatives are potent herbicides demonstrating a broad spectrum of weed control. 2. The compound of claim 1 , wherein the compound is6-amino-5-chloro-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-caroxylic acid methyl ester6-amino-5-chloro-2-(2-fluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester;6-amino-5-chloro-2-(2,3-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester;6-amino-5-chloro-2-(2,3-difluoro-4-trifluoromethylphenyl)pyrimidine-4-carboxylic acid;6-amino-5-chloro-2-(2,5-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester;6-amino-5-chloro-2-(4,5-dichloro-2-fluorophenyl)pyrimidine-4-carboxylic acid methyl ester;6-amino-5-chloro-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-carboxylic acid;6-amino-5-chloro-2-(2,3-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid;6-amino-5-chloro-2-(2,3-difluoro-4-trifluoromethylphenyl)pyrimidine-4-carboxylic acid;6-amino-5-chloro-2-(4,5-dichloro-2-fluorophenyl)pyrimidine-4-carboxylic acid;6-amino-5-chloro-2-(2,5-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid; or6-amino-5-chloro-2-(4-chloro-2,5-difluorophenyl)-pyrimidine-4-carboxylic acid methyl ester.3. The compound of claim 1 , wherein the compound is 6-amino-5-chloro-2-(4-chloro-2 claim 1 ,3-difluorophenyl)pyrimidine-4-caroxylic acid methyl ester.4. The compound of claim 1 , wherein compound is 6-amino-5-chloro-2-(2-fluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester.5. The compound of claim 1 , wherein the compound is 6-amino-5-chloro-2-(2 claim 1 ,3-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester.6. The compound of claim 1 , wherein the compound is 6-amino-5-chloro-2-(2 claim 1 ,3-difluoro-4-trifluoromethylphenyl)pyrimidine-4-carboxylic acid.7. The compound of claim 1 , wherein the compound is 6-amino-5-chloro-2-(2 claim 1 ,5-difluoro-4-methylphenyl)pyrimidine-4-carboxylic acid methyl ester.8. The compound of claim ...

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Номер записи: 7
16-05-2013 дата публикации

METHOD FOR PRODUCING CARBOXYLIC ACID AMIDE

Номер: US20130123505A1
Автор: Hirata Norihiko, KIMURA Takahiro, Tomokawa Junichi
Принадлежит:

A carboxamide can be produced in a high yield by a method for producing a carboxamide, for example, represented by formula (4): 1. A method for producing a carboxamide , the method comprising allowing a carboxylic acid ester , an amine , and a formamide compound corresponding to the amine to react in the presence of a metal alkoxide.3. The method according to claim 2 , wherein the step is a step of performing the reaction in a solvent.4. The method according to claim 3 , wherein the solvent is an alcohol solvent.5. The method according to claim 2 , wherein the metal alkoxide is an alkali metal alkoxide.6. The method according to claim 2 , wherein the step is a step performed under an increased pressure condition.7. The method according to claim 2 , wherein Rin each of formulae (2) claim 2 , (3) and (4) is a hydrogen atom or a C-Calkyl group.8. The method according to claim 2 , wherein Rin formula (1) is a C-Calkyl group.9. The method according to claim 3 , wherein the metal alkoxide is an alkali metal alkoxide.10. The method according to claim 3 , wherein the step is a step performed under an increased pressure condition. The present invention relates to a method for producing a carboxamide.Carboxamides are important compounds as a variety of chemical products such as active ingredients of medicines and pesticides, and electronic materials, and synthetic intermediates thereof (see, for example, WO2004/065374).In WO2004/065374 is disclosed a method in which ethyl 4,5-bis(4-methoxyphenyl)-1,3-oxazole-2-carboxylate, which is a carboxylic acid ester, is allowed to react with formamide in the presence of sodium methoxide, which is a metal alkoxide, to give 4,5-bis(4-methoxyphenyl)-1,3-oxazole-2-carboxamide, which is a carboxamide, in a yield of 71.9% (see Example 2).However, the method is not necessarily satisfactory in the yield of the carboxamide to be obtained.Thus, new methods by which a carboxamide can be produced from a carboxylic acid ester in a high yield have ...

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Номер записи: 8
30-05-2013 дата публикации

TRYPTOPHAN HYDROXYLASE INHIBITORS FOR THE TREATMENT OF METASTATIC BONE DISEASE

Номер: US20130137635A1
Автор: Sands Arthur Thomas
Принадлежит: LEXICON PHARMACEUTICALS, INC.

This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease. 2. The use of claim 1 , wherein the metastatic bone disease is osteosclerotic (osteoblastic).3. The use of claim 2 , wherein the metastatic bone disease is bone metastases of prostate cancer.4. The use of claim 3 , wherein the compound is used in combination with a therapeutically or prophylactically effective amount of a second drug.5. The use of claim 4 , wherein the second drug is a luteinizing hormone-releasing hormone agonist (e.g. claim 4 , leuprolide claim 4 , goserelin claim 4 , buserelin); an antiandrogen (e.g. claim 4 , flutamide claim 4 , nilutamide); or an adrenal gland inhibitor (e.g. claim 4 , ketoconazole claim 4 , aminoglutethimide).6. The use of claim 5 , wherein the second drug is mitoxantrone claim 5 , estramustine claim 5 , doxorubicin claim 5 , etoposide claim 5 , vinblastine claim 5 , paclitaxel claim 5 , carboplatin claim 5 , or vinorelbine.11. The pharmaceutical composition of claim 10 , wherein the second drug is mitoxantrone claim 10 , estramustine claim 10 , doxorubicin claim 10 , etoposide claim 10 , vinblastine claim 10 , paclitaxel claim 10 , carboplatin claim 10 , or vinorelbine. This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease.The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior. In peripheral tissues, serotonin is implicated in the regulation of vascular tone, gut motility, primary hemostasis, and cell-mediated immune responses. Walther, D. J., et al., 299:76 (2003). Some evidence also suggests that serotonin can affect bone growth. See, e.g., ...

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Номер записи: 9
06-06-2013 дата публикации

METHOD FOR PREPARING ROSUVASTATIN CALCIUM INTERMEDIATE

Номер: US20130143908A1
Автор: LIN Wenqing, YANG Peng, ZHENG Hongjie
Принадлежит: PORTON FINE CHEMICALS LTD.

A method for preparing a rosuvastatin calcium intermediate represented by formula I. The method includes: hydrolyzing an ester compound represented by formula II (in which, R represents C1-C5) in the presence of a metal compound to obtain a carboxylic acid compound represented by formula III; and reducing the carboxylic acid compound in the presence of a reductant. 2. The method of claim 1 , wherein in step a) claim 1 , the metallic compound is LiOH or a hydrate thereof.3. The method of claim 1 , wherein in step b) claim 1 , the reductant is a borane or a hydroboron and Lewis acid reduction system.4. The method of claim 3 , wherein the hydroboron and Lewis acid reduction system is selected from the group consisting of a system comprising potassium borohydride and boron trifluoride diethyl etherate; a system comprising sodium borohydride and boron trifluoride diethyl etherate; a system comprising lithium borohydride and boron trifluoride diethyl etherate; a system comprising potassium borohydride and HSO; a system comprising potassium borohydride and ZnCl; a system comprising potassium borohydride and AlCl; a system comprising potassium borohydride and I; a system comprising potassium borohydride and CFCOOH; a system comprising potassium borohydride and HCOOH; a system comprising potassium borohydride and MsOH; a system comprising potassium borohydride and CHCOOH; a system comprising potassium borohydride and NiCl; a system comprising zinc borohydride and HSO; a system comprising zinc borohydride and ZnCl; a system comprising zinc borohydride and AlCl; a system comprising zinc borohydride and I; a system comprising zinc borohydride and CFCOOH; a system comprising zinc borohydride and HCOOH; a system comprising zinc borohydride and MsOH; a system comprising zinc borohydride and CHCOOH; a system comprising zinc borohydride and NiCl; a system comprising sodium borohydride and HSO; a system comprising sodium borohydride and ZnCl; a system comprising sodium borohydride ...

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Номер записи: 10
13-06-2013 дата публикации

IMAGING TUBERCULOSIS WITH PYRAZINAMIDE CONTRAST AGENTS

Номер: US20130149249A1
Автор: Hegde Ravi, Kuniyil Kulangara Vijaya Raj
Принадлежит: GE HEALTHCARE LIMITED

The present invention provides novel in vivo imaging agents useful for detecting the presence of mycobacteria using in vivo imaging methods. Also provided by the present invention is a precursor compound useful in the synthesis of the in vivo imaging agents of the invention, and a method to obtain the in vivo imaging agent of the invention using said precursor compound. Methods of in vivo imaging and diagnosis in which the in vivo imaging agent of the invention finds use are also provided. 2) The in vivo imaging agent as defined in wherein said metal ion suitable for in vivo imaging is either a radioactive metal ion or a paramagnetic metal ion.3) The in vivo imaging agent as defined in wherein said radioactive metal ion is a gamma-emitting radioactive metal ion selected from Tc claim 2 , In claim 2 , In claim 2 , and Ga.4) The in vivo imaging agent as defined in wherein said radioactive metal ion is Tc.5) The in vivo imaging agent as defined in wherein said radioactive metal ion is a positron-emitting radioactive metal ion selected from Cu claim 2 , V claim 2 , Fe claim 2 , Co claim 2 , Tc and Ga.6) The in vivo imaging agent as defined in wherein said paramagnetic metal ion is selected from Gd(III) claim 2 , Mn(II) claim 2 , Cu(II) claim 2 , Cr(III) claim 2 , Fe(III) claim 2 , Co(II) claim 2 , Er(II) claim 2 , Ni(II) claim 2 , Eu(III) and Dy(III).7) The in vivo imaging agent as defined in wherein Chis:(a) diaminedioximes;{'sub': '3', '(b) NS ligands having a thioltriamide donor set;'}{'sub': 2', '2, '(c) NSligands having a diaminedithiol donor set;'}{'sub': '4', '(d) Nligands which are open chain or macrocyclic ligands having a tetramine, amidetriamine or diamidediamine donor set; or,'}{'sub': 2', '2, '(e) NOligands having a diaminediphenol donor set.'}8) A pharmaceutical composition comprising the in vivo imaging agent as defined in together with a pharmaceutically acceptable carrier.11) The method as defined in wherein said source of metal ion suitable for in vivo ...

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Номер записи: 11
04-07-2013 дата публикации

PYRIMIDINE COMPOUNDS AND THEIR USES

Номер: US20130172350A1
Автор: Balasubramanian Gopalan, Parameswaran Venkatesan, Saxena Sanjeev, SHARMA Ganapavarapu, Vishwakarma Santosh
Принадлежит: Orchid Chemicals and Pharmaceuticals Limited

Pyrimidine compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites and prodrugs thereof, are useful are useful as PDE4 inhibitors and are useful for treating PDE4 mediated diseases and in the treatment of immunological diseases, inflammation, pain disorder, rheumatoid arthritis; osteoporosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; atherosclerosis; cancer; cachexia; ischemic-induced cell damage; pancreatic beta cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; ARDS; psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; muscle degeneration; asthma; COPD; bone resorption diseases; multiple sclerosis; sepsis; septic shock; toxic shock syndrome and fever. 4. The composition of in the form of a tablet claim 3 , capsule claim 3 , powder claim 3 , syrup claim 3 , solution or suspension.6. A method of treatment of rheumatoid arthritis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.7. A method of treatment of osteoporosis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.8. A method of treatment of multiple myeloma in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.9. A method of treatment of uveitis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.10. A method of treatment of atheroscelorsis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.11. A method of treatment of osteoarthritis in a mammal comprising administering an effective amount of a compound as claimed in to the ...

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Номер записи: 12
18-07-2013 дата публикации

Method for preparing pharmaceutical compositions intended for oral administration comprising one or more active ingredients and the compositions comprising same

Номер: US20130183382A1
Автор: Axelle Lesot, Gael Lamoureux
Принадлежит: SANOFI SA

The present invention relates to fexofenadine granules, to a composition containing them and to a process for the hot-melt coating of fexofenadine. The process for the hot-melt coating of fexofenadine allows efficient masking of its bitter taste without, however, unacceptably slowing down its dissolution.

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Номер записи: 13
18-07-2013 дата публикации

Novel Phenylamino Isonicotinamide Compounds

Номер: US20130184314A1
Автор: Askew, Goutopoulos Andreas, Jr. Benny C., Liu-Bujalski Lesley, Yu Henry
Принадлежит: Merck Patent GmBH

The invention provides novel compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer, restenosis and inflammation. 113-. (canceled)15. A method for treating hyperproliferative diseases related to the hyperactivity of MEK as well as diseases modulated by the MEK cascade in mammals , comprising administering to a subject a compound according to in which radicals not designated in greater detail have the meaning indicated for the Formula (I) according to but in which:in Subformula IAX is NH,{'sup': '1', 'Ris Hal, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, Hal, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula IBX is NH,{'sup': '1', 'Ris Hal,'}{'sup': '2', 'Ris hydrogen or Hal,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula ICX is NH,{'sup': '1', 'Ris F, Cl, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, I, Br, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or Hal,'}{'sup': '4', 'Ris hydrogen or Hal,'}{'sup': 5', '6, 'R, Rare OH,'}Hal is F, Cl, Br or I,in Subformula IDX is NH,{'sup': '1', 'Ris F, Cl, methyl or ethyl,'}{'sup': '2', 'Ris hydrogen, I, Br, methoxy or acetylene,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IEX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IFX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen or F,'}{'sup': '4', 'Ris hydrogen or Cl,'}{'sup': 5', '6, 'R, Rare OH,'}in Subformula IGX is NH,{'sup': '1', 'Ris F or Cl,'}{'sup': '2', 'Ris I or Br,'}{'sup': '3', 'Ris hydrogen,'}{'sup': '4', 'Ris hydrogen,'}{'sup': 5', '6, 'R, Rare OH,'}and in ...

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Номер записи: 14
01-08-2013 дата публикации

PREPARATION METHOD OF ROSUVASTATIN CALCIUM AND ITS INTERMEDIATES

Номер: US20130197224A1
Автор: CHEN Benshun, JIN Xiaofeng, WANG Bing, ZOU Lin
Принадлежит: CHANGZHOU PHARMACEUTICAL FACTORY

A preparation method of rosuvastatin calcium (Formula 1), which can be used for the production of medicament lowering the levels of LDL-cholesterol and triglycerides in vivo, is provided. Such preparation method is suitable for industrial production. Furthermore, the intermediate crystallines used in the preparation method are provided. 2. The method of claim 1 , wherein the crystalline intermediate is chosen from (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-methyl heptenoate claim 1 , (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-isopentyl heptenoate claim 1 , and (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-isopentyl heptenoate3. The method of claim 2 , wherein the crystalline intermediate is (3R claim 2 ,5S claim 2 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 2 ,5-dihydroxyl-6-methyl heptenoate claim 2 , and the crystalline intermediate has a spectrum of powder XRD with peak values at 2θ=8.7 claim 2 , 9.3 claim 2 , 9.6 claim 2 , 17.4 claim 2 , 18.0 claim 2 , 19.5 claim 2 , 21.7 claim 2 , 24.4 claim 2 , 24.7 and 26.3.4. The method of claim 3 , wherein the crystalline intermediate is prepared from (3R claim 3 ,5S claim 3 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 3 ,5-dihydroxyl-6-methyl heptenoate following step (c).5. The method of claim 4 , wherein the crystalline intermediate is prepared by recrystallizing (3R claim 4 ,5S claim 4 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 4 ,5-dihydroxyl-6-methyl heptenoate in the presence of a solvent comprising ethyl ether.6. The crystalline intermediate of being used for the ...

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Номер записи: 15
08-08-2013 дата публикации

NOVEL COMPOUNDS, USE AND PREPARATION THEREOF

Номер: US20130203774A1
Автор: Jensen Annika Jenmalm, Lehmann Fredrik, Nilsson Bjorn M., Nordling Erik, Parrow Vendela
Принадлежит: AKINION PHARMACEUTICALS AB

The present invention relates to compounds of the general formula (I) wherein R, Rand Rare as defined herein, which can act as inhibitors of protein kinases, specially the Fms-like tyrosine kinase 3 (FLT3). The invention also relates to the use of the compounds in therapy, pharmaceutical compositions comprising the compounds and the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of hematological malignancies, such as AML, MLL, T-ALL, B-ALL and CMML, myeloproliferative disorders, other proliferative disorders like cancer, autoimmune disorders and skin disorders like psoriasis and atopic dermatitis. 124-. (canceled)26. A pharmaceutical formulation comprising a compound according to .27. A compound according to for use in therapy.28. A method for the treatment of one or more conditions selected from the group consisting of haematological malignancies claim 25 , myeloproliferative disorders claim 25 , cancer claim 25 , autoimmune disorders claim 25 , and skin disorders claim 25 , said method comprising administering a therapeutically effective amount of the compound according to to a human in need thereof.29. The method of claim 28 , wherein the condition is a haematological malignancy.30. The method of claim 29 , wherein the haematological malignancy is selected from the group consisting of acute myeloic leukemia (AML) claim 29 , mixed lineage leukemia (MLL) claim 29 , T-cell type acute lymphocytic leukemia (T-ALL) claim 29 , B-cell type acute lymphocytic leukemia (B-ALL) and chronic myelo-monocytic leukemia (CMML).31. The method of claim 30 , wherein the haematological malignancy is acute myeloic leukemia (AML).32. A pharmaceutical composition comprising a compound according to claim 25 , in conjunction with another molecularly targeted agent.33. The pharmaceutical composition according to claim 32 , wherein the molecularly targeted agent is a conventional cytotoxic agent claim 32 , or a compound used in postchemotherapy ...

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Номер записи: 16
08-08-2013 дата публикации

Co-crystals of pyrimethanil or cyprodinil

Номер: US20130203792A1
Автор: Christer Bjorn Aakeroy, James Owen Forrest, Neil George, Rebecca Claire Burton
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to co-crystals of cyprodinil or pyrimethanil and a co-crystal forming compound which has at least one imide and/or oxime functional group.

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Номер записи: 17
08-08-2013 дата публикации

Process for making bortezomib and intermediates for the process

Номер: US20130203988A1
Автор: Jakub Castulik, Miroslav Zabadal
Принадлежит: Synthon BV

The invention relates to processes of making bortezomib of formula (1) enantiomers thereof and/or intermediates thereof, comprising at least one step of coupling a carboxylic acid with an amine, wherein the coupling step is performed in a presence of the compound of formula (8), wherein A is C1-C6 alkyl group, preferably wherein A is n-propyl group.

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Номер записи: 18
15-08-2013 дата публикации

Method for preparing substituted N-(3-amino-quinoxalin-2-yl)-sulfonamides and their intermediates N-(3-chloro-quinoxalin-2-yl)-sulfonamides

Номер: US20130211076A1
Автор: Pohin Danig, Swinnen Dominique
Принадлежит: MERCK SERONO S.A. GENEVA

The present invention provides a new synthesis for preparing N-(3-amino-quinoxalin-2-yl)-sulfonamides of general formulae (I) or (I′) and intermediates sulfonamides of formula (II) or (II′): 2. The process as defined in wherein the polar aprotic solvent is selected from DMA claim 1 , DMF claim 1 , NMP and DMSO.3. The process of wherein the alkali metal hydroxide is selected from LiOH and KOH.4. The process of wherein the step b) is performed in the presence of a pyridine base.5. The process of wherein the pyridine base is selected from pyridine claim 4 , methyl pyridine claim 4 , and 2 claim 4 ,6-di-methylpyridine.6. The process of wherein the pyridine base is lutidine.7. The process of wherein step b) is performed in a polar solvent.8. The process of wherein the polar solvent is selected from DMA claim 7 , DMF claim 7 , NMP claim 7 , DMSO or alcohol. The present invention provides a new synthesis for preparing N-(3-amino-quinoxalin-2-yl)-sulfonamides of general formula (I) and its intermediate N-(3-chloro-quinoxalin-2-yl)-sulfonamides of formula (II). The compounds of formulae (I) and (II) are useful building blocks, in particular in the synthesis of drugs.The present invention is related to a new synthesis for preparing N-(3-amino-quinoxalin-2-yl)-sulfonamides of general formulae (I) and (I′), and their intermediates N-(3-chloro-quinoxalin-2-yl)-sulfonamides of formulae (II) and (II′):Ris selected from the group consisting of A, C-C-cylcoalkyl, Het, and Ar. Ris selected from the group consisting of Ar and Het. Ar denotes a monocyclic or bicyclic, aromatic carbocyclic ring having 6 to 14 carbon atoms, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, CF, OCF, NO, CN, perfluoroalkyl, A, —OR, —NHR, —COR, —CONHR, —CON(R), —NRCOR, —NRCOR, —NRSOA, NRCONR′R″, —COOR, —SOA, —SONRA, —SOHet, —SONRHet, Ar, Het, —NRSONRHet, COHet, COAr, or C-C-cycloalkyl. Het denotes a monocyclic or bicyclic saturated, unsaturated or aromatic heterocyclic ring ...

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Номер записи: 19
15-08-2013 дата публикации

PROCESS FOR THE PREPARATION OF ENANTIOMERIC FORMS OF 2,3-DIAMINOPROPIONIC ACID DERIVATIVES

Номер: US20130211085A1
Автор: GRAF Claus-Dieter, RIEKE-ZAPP Joerg
Принадлежит: SANOFI

The disclosure relates to a process for the preparation of the enantiomeric forms of 2,3-diaminopropionic acid derivatives of formula I, 2. The process as claimed in claim 1 , wherein the enantiomerically pure auxiliary used is (S)-1-phenylethylamine claim 1 , (R)-1-phenylethylamine claim 1 , (S)-1-phenylpropylamine claim 1 , (R)-1-phenylpropylamine claim 1 , (S)-1-naphthylethylamine claim 1 , (R)-1-naphthylethylamine claim 1 , (S)-1-cyclohexylethylamine claim 1 , (R)-1-cyclohexylethylamine claim 1 , (S)-1-cyclopropylethylamine or (R)-1-cyclopropylethylamine.3. The process as claimed in claim 1 , wherein the organic solvent used is n-butyl acetate claim 1 , ethyl acetate claim 1 , isopropyl acetate claim 1 , diisopropyl ether or methyl tert-butyl ether.4. The process as claimed in claim 2 , wherein the organic solvent used is n-butyl acetate claim 2 , ethyl acetate claim 2 , isopropyl acetate claim 2 , diisopropyl ether or methyl tert-butyl ether.5. The process as claimed in claim 1 , wherein the molar ratio of the compound of formula II to the enantiomerically pure auxiliary is from 0.5 to 1.1.6. The process as claimed in claim 2 , wherein the molar ratio of the compound of formula II to the enantiomerically pure auxiliary is from 0.5 to 1.1.7. The process as claimed in claim 1 , wherein the compound of formula I is obtained wherein:R1 is a hydrogen atom, F, Cl, I or Br;R2 is phenyl, pyridinyl, pyrimidinyl or thiazolyl, wherein phenyl, pyridinyl, pyrimidinyl and thiazolyl are unsubstituted or substituted by fluorine or chlorine; and{'sub': 3', '3, 'R3 is phenyl, methyl or —O—C(CH).'}8. The process as claimed in claim 2 , wherein the compound of formula I is obtained wherein:R1 is a hydrogen atom, F, Cl, I or Br;R2 is phenyl, pyridinyl, pyrimidinyl or thiazolyl, wherein phenyl, pyridinyl, pyrimidinyl and thiazolyl are unsubstituted or substituted by fluorine or chlorine; and{'sub': 3', '3, 'R3 is phenyl, methyl or —O—C(CH).'}9. The process as claimed in claim 3 , ...

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Номер записи: 20
22-08-2013 дата публикации

MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO

Номер: US20130217706A1
Автор: Chen Weichao, Kramer Bryan A., Sadeque Abu J.M., Shifrina Anna, SHIN Young-Jun, Tran Thuy-Anh, Vallar Pureza, Zou Ning
Принадлежит: ARENA PHARMACEUTICALS, INC.

The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease; and other diseases. 238-. (canceled)4142-. (canceled)43. A compound according to selected from the following compounds and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(((1r,4r)-4-((3-benzhydrylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3,3-diphenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(3-fluorophenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((1-methyl-3,3-diphenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((diphenylcarbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(3-chlorophenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1s,4s)-4-((diphenylcarbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(4-fluorophenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1s,4s)-4-((3,3-diphenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(2-fluorophenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(4-chlorophenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-phenyl-3-m-tolylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-phenyl-3-p-tolylureido)methyl)cyclohexyl)methoxy) acetic acid;2-(((1r,4r)-4-(((3-methoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3,3-di p-tolylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3,3-di m-tolylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3-(3-methoxyphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy)acetic acid;2-(((1r,4r)-4-((3 ...

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Номер записи: 21
22-08-2013 дата публикации

MEGLUMINE SALT OF 6-FLUORO-3-HYDROXY-2-PYRAZINE CARBOXAMIDE

Номер: US20130217708A1
Автор: Nakamatsu Namika, Nakashima Takayoshi, Takakura Keiko, Takeshima Sakiko
Принадлежит: Toyama Chemical Co., Ltd.

A preparation replete with a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazine carboxamide has superior solubility, and is useful as a preparation for injection. 1: A meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or a hydrate thereof.2: The meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or the hydrate thereof of claim 1 , in a crystal form.3: The meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or the hydrate thereof of claim 1 , in an amorphous form.4: An injectable preparation comprising the meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or the hydrate thereof of .5: The injectable preparation of claim 4 , wherein the meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or the hydrate thereof is in a crystal form.6: The injectable preparation of claim 4 , wherein the meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or the hydrate thereof is in an amorphous form.7: The injectable preparation of claim 4 , further comprising an amino acid and a saccharide claim 4 , or an amino acid and a sugar alcohol.8: A lyophilized preparation comprising a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide.9: The lyophilized preparation of claim 8 , wherein the meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide is in a crystal form.10: The lyophilized preparation of claim 8 , wherein the meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide is in an amorphous form.11: The lyophilized preparation of claim 8 , further comprising an amino acid and a saccharide claim 8 , or an amino acid and a sugar alcohol.12: A process for producing a lyophilized preparation comprising a crystal of a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide claim 8 , the process comprising:(1) cooling an aqueous solution comprising 6-fluoro-3-hydroxy-2-pyrazinecarboxamide and meglumine to produce a frozen product;(2) increasing the temperature of the frozen product;(3) cooling the frozen product again; and(4) carrying ...

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Номер записи: 22
29-08-2013 дата публикации

Crystalline Form of Bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] Calcium Salt

Номер: US20130225622A1
Автор: Booth Rebecca Jane, Cittern Peter Anthony, Crabb Jeffrey Norman, Hornbury John, Jones David Wyn Calvert
Принадлежит: AstraZeneca UK Limited

Two polymorphic forms of bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt, processes for making them and their use as HMG Co-A reductase inhibitors are described. 2. The crystalline hydrated form as claimed in with an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.3 claim 1 , 8.8 claim 1 , 13.1 claim 1 , 13.7 claim 1 , 21.5 claim 1 , 22.8 and 28.9°.3. The crystalline hydrated form as claimed in with an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.3 claim 1 , 8.8 claim 1 , 13.1 claim 1 , 13.7 claim 1 , 15.2 claim 1 , 15.8 claim 1 , 17.5 claim 1 , 21.5 claim 1 , 21.9 claim 1 , 22.8 claim 1 , 24.5 and 28.9°.4. The crystalline hydrated form as claimed in claim 1 , which contains about 9-10% water.5. The crystalline hydrated form as claimed in having an X-ray powder diffraction pattern substantially as shown in .7. The crystalline form as claimed in having an X-ray powder diffraction pattern substantially as shown in .8. A pharmaceutical composition comprising the crystalline form as claimed in and a pharmaceutically acceptable carrier.9. A process for formation and amorphous bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R claim 1 ,5S)-3 claim 1 ,5-dihydroxyhept-6-enoic acid] calcium salt comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'isolating from a solution the crystalline form as claimed in ; and'}subsequently converting the crystalline form to an amorphous form.10. The process as claimed in comprisingmixing a solution contain [(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt with a slurry of the crystalline form of formula 1 having an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=8.8, 13.1 and 21.5° or formula 1 having an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.4, 7 ...

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Номер записи: 23
05-09-2013 дата публикации

ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE

Номер: US20130231342A1
Автор: Estirate-Martinez Maria de los Ángeles, Fyfe Matthew Colin Thor, MARTINELL PEDEMONTE Marc, Muñoz Alberto Ortega, TIRAPU FERNANDEZ DE LA CUESTA Iñigo
Принадлежит: Oryzon Fenomics S.A.

The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX). 2. The compound of wherein (A) is an aryl group or a heteroaryl group claim 1 , wherein said aryl group or said heteroaryl group has n substituents (R3).3. The compound of wherein (A) is phenyl claim 1 , pyridinyl claim 1 , thiophenyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , or thiazolyl claim 1 , and further wherein (A) has n substituents (R3).4. The compound of wherein (A) is phenyl or pyridyl claim 1 , and further wherein said phenyl or said pyridyl has n substituents (R3).5. The compound of wherein (A) has 0 substituents (R3).6. The compound of wherein (B) is —O—CH-phenyl or phenyl claim 1 , and further wherein said phenyl or the phenyl moiety comprised in said —O—CH-phenyl has n substituents (R2).78-. (canceled)9. The compound of wherein (B) has 0 claim 1 , 1 or 2 substituents (R2).10. (canceled)11. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiadiazolyl claim 1 , triazinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , pyridinyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl claim 1 , said oxazolyl claim 1 , said isoxazolyl claim 1 , said thiadiazolyl claim 1 , said triazinyl claim 1 , said pyridazinyl claim 1 , said pyrazinyl claim 1 , said pyridinyl or said pyrimidinyl has one substituent (R1).12. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl or said pyrimidinyl has one substituent (R1).13. The compound of wherein (D) is oxadiazolyl ...

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Номер записи: 24
12-09-2013 дата публикации

2-(POLY-SUBSTITUTED ARYL)-6-AMINO-5-HALO-4-PYRIMIDINECARBOXYLIC ACIDS AND THEIR USE AS HERBICIDES

Номер: US20130237422A1
Автор: Balko Terry W., Epp Jeffrey B., Ruiz James M., Schmitzer Paul R., Siddall Thomas L., Yerkes Carla N.
Принадлежит: DOW AGROSCIENCES LLC

6-Amino-5-halo-4-pyrimidinecarboxylic acids having poly-substituted aryl substituents in the 2-position, and their amine and acid derivatives, are potent herbicides demonstrating a broad spectrum of weed control. 20. A herbicidal composition comprising a herbicidally effective amound of a compound of and an agriculturally acceptable adjuvant or carrier.21. A method of controlling undesirable vegetation comprising (a) post-emergently contacting the vegetation or locus thereof or (b) pre-emergently contacting the area where the undesirable vegetation is to be controlled a herbicidally effective amound of the compound of .22. The method of claim 21 , wherein the undesirable vegetation is controlled by post-emergently contacting the vegetation of locus thereof.23. The method of claim 21 , wherein the undesirable vegetation is controlled by pre-emergently contacting the area where the undesirable vegetation is to be controlled.24. The method of claim 21 , wherein (a) or (b) is performed in the presence of rice claim 21 , wherein the rice is not injured.25. The method of claim 24 , wherein the rice is not injured one to twenty days after performing (a) or (b).26. The method of claim 21 , wherein (a) or (b) is performed in the presence of rice claim 21 , wherein the rice is injured to a lesser extent than the undesirable vegetation.27. The method of claim 21 , wherein (a) or (b) is performed in the presence of wheat or barley claim 21 , wherein the wheat or barley is not injured.28. The method of claim 27 , wherein the wheat or barley is not injured one to twenty days after performing (a) or (b).29. The method of claim 21 , wherein (a) or (b) is performed in the presence of wheat or barley claim 21 , wherein the wheat or barley is injured to a lesser extent than the undesirable vegetation.30. The method of claim 21 , wherein the undesirable vegetation is CHEAL claim 21 , ABUTH claim 21 , HELAN claim 21 , LAMPU claim 21 , PAPRH claim 21 , VERPE claim 21 , SCPJU claim 21 , ...

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Номер записи: 25
19-09-2013 дата публикации

Methods Of Administering High Concentrations Of Nitric Oxide

Номер: US20130239963A1
Автор: Brahm Goldstein, Douglas Stuart Greene
Принадлежит: INO THERAPEUTICS LLC

Described are methods of administering therapeutic gases comprising high concentrations of nitric oxide, particularly concentrations above 2,000 ppm. The therapeutic gas may be administered at a certain dosing rate, such as less than 166 micrograms of nitric oxide per second. Also described are methods of administering a therapeutic gas comprising nitric oxide to a patient, wherein a dose of nitric oxide is administered from a portable device that includes a delivery system and a mini-cylinder. Methods of intermittent administration of nitric oxide pulses are also described.

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Номер записи: 26
19-09-2013 дата публикации

Process for the preparation of pazopanib using novel intermediate

Номер: US20130245262A1
Автор: BANDI Parthasaradhi Reddy, Bandi Vamsi Krishna, Dasari Muralidhara Reddy, KURA Rathnakar Reddy, Thungathurthy Srinivasa Rao
Принадлежит: HETERO RESEARCH FOUNDATION

The present invention provides a commercially viable process for preparing pazopanib and its pharmaceutically acceptable acid addition salts thereof in high yields using novel intermediate. The present invention also provides a process for the purification of pazopanib hydrochloride.

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Номер записи: 27
19-09-2013 дата публикации

Process for the preparation of pyrimidine derivatives

Номер: US20130245263A1
Автор: Jan Schultz, Reinhard Karge
Принадлежит: DSM IP ASSETS BV

A process for the preparation of 5-substituted 4-amino-2-methylpyrimidines of the formula wherein R is CONH 2 or CN, and of acid addition salts thereof, characterized in that a compound of formula H 2 N—CH═C(R) CN (II) is reacted with acetimidic acid methyl ester or an acid addition salt thereof and that, if desired, a compound of formula I is transferred into an acid addition salt, and the transformation of a compound of formula II wherein R is CONH 2 into a compound of formula II wherein R is CN by treatment with POCl 3 .

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Номер записи: 28
19-09-2013 дата публикации

PYRAZINO[2,3-D]ISOXAZOLE DERIVATIVE

Номер: US20130245264A1
Автор: HANAKI Naoyuki, Murakami Takeshi, NAITOU Hiroyuki, NAKAMURA Kouki, WATANABE Katsuyuki
Принадлежит:

The object of the present invention is to provide a compound which is useful as a production intermediate of pyrazine carboxamide derivative such as 6-fluoro-3-hydroxy-2-pyrazine carboxamide. The present invention provides a pyrazino[2,3-d]isoxazole derivative represented by the formula (I): 2. The pyrazino[2 claim 1 ,3-d]isoxazole derivative according to claim 1 , wherein Y represents —C(═O)R where R represents an alkoxy group or an amino group claim 1 , and the alkoxy group and amino group may be optionally substituted.3. The pyrazino[2 claim 1 ,3-d]isoxazole derivative according to claim 1 , wherein X represents a hydroxyl group claim 1 , a chlorine atom or a fluorine atom.4. The pyrazino[2 claim 2 ,3-d]isoxazole derivative according to claim 2 , wherein X represents a hydroxyl group claim 2 , a chlorine atom or a fluorine atom.5. The pyrazino[2 claim 1 ,3-d]isoxazole derivative according to claim 1 , wherein X represents a fluorine atom or a chlorine atom claim 1 , and Y represents —C(═O)R where R represents an optionally substituted alkoxy group.6. The pyrazino[2 claim 1 ,3-d]isoxazole derivative according to claim 1 , wherein X represents a fluorine atom or a chlorine atom claim 1 , and Y represents —C(═O)R where R represents a methoxy group claim 1 , an ethoxy group claim 1 , an n-propoxy group claim 1 , an isopropoxy group claim 1 , or an n-butoxy group.10. The production method according to claim 8 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents an optionally substituted alkoxy group.11. The production method according to claim 9 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents an optionally substituted alkoxy group.12. The production method according to claim 8 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents a methoxy group claim 8 , an ethoxy group claim 8 , an n-propoxy group claim 8 , an isopropoxy group claim 8 , or an n-butoxy group.13. The ...

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Номер записи: 29
26-09-2013 дата публикации

5,6-BISARYL-2-PYRIDINE-CARBOXAMIDE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC APPLICATION THEREOF AS UROTENSIN II RECEPTOR ANTAGONISTS

Номер: US20130252974A1
Автор: Altenburger Jean-Michel, Fossey Valérie, Galtier Daniel, Petit Frédéric
Принадлежит: SANOFI

The present invention relates to 5,6-bisaryl-2-pyridinecarboxamides, to their preparation and to their therapeutic use as urotensin II receptor antagonists. 2. The compound of claim 1 , wherein:R4 represents a hydrogen atom;W represents a halogen atom;Z represents a (C1-C4) alkylene group;either, R1 represents a hydrogen atom and R2 represents a (C1-C4) alkyl group, or R1 and R2 form, together with the carbon atom to which they are attached, a monocyclic or polycyclic system selected from a (C3-C8) cycloalkyl group and a bridged tetracyclic group, wherein said monocyclic or polycyclic system is optionally substituted with one or more hydroxyl groups;either R3 represents a group C(O)R5, with R5 representing a (C1-C4) alkoxy group optionally substituted with a (C1-C4) alkoxy group or a group NR6R7, with R6 and R7, independently of each other, representing a hydrogen atom or a (C1-C4) alkyl, (C3-C5) cycloalkyl, (C1-C4) alkylsulfonyl, or haloalkyl group,{'sub': '2', 'or R3 represents a group CHXR8 in which X represents an oxygen atom and R8 represents a hydrogen atom or a (C1-C4) alkyl group,'}or R3 represents a nitrile group (CN).3. The compound of claim 1 , wherein:X represents a nitrogen atom and Y represents a nitrogen atom or —CR4-, in which R4 represents a hydrogen atom;A represents said fused aryl, unfused aryl, or heteroaryl group, wherein said aryl or heteroaryl group is optionally substituted with one or more groups selected from halogen atom, (C1-C4) alkyl, (C3-C5) cycloalkyl, (C1-C4) alkoxy, and haloalkoxy;W represents a halogen atom;Z represents a (C1-C4) alkylene group; andeither, R1 represents a hydrogen atom and R2 represents a (C1-C4) alkyl group, or R1 and R2 form, together with the carbon atom to which they are attached, a (C3-C8) cycloalkyl group optionally substituted with one or more hydroxyl groups or an adamantyl group;either R3 represents a group C(O)R5 with R5 representing a (C1-C4) alkoxy group optionally substituted with a (C1-C4) alkoxy ...

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Номер записи: 30
03-10-2013 дата публикации

Novel Substituted Bicyclic Aromatic Compounds as S-Nitrosoglutathione Reductase Inhibitors

Номер: US20130261122A1
Автор: Qiu Jian, Stout Adam, Sun Xicheng
Принадлежит: N30 Pharmaceuticls, Inc.

The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 4. The compound of wherein Ris hydrogen.5. The compound of where Ris hydrogen.7. The compound of wherein{'sub': '1', 'Ris selected from the group consisting of H and F;'}{'sub': '2a', 'Ris selected from the group consisting of H, F, Cl, Br, and cyano;'}{'sub': '2b', 'Ris selected from the group consisting of H, F, and Cl;'}{'sub': '2c', 'Ris H; and'}{'sub': '4', 'Ris selected from the group consisting of H, F, Cl, and cyano.'}8. The compound of wherein Ris selected from the group consisting of F and Cl.9. The compound of wherein Ris selected from the group consisting of F claim 6 , Cl claim 6 , Br claim 6 , Me claim 6 , OCH claim 6 , and cyano.10. The compound of wherein Ris selected from the group consisting of F claim 6 , Cl claim 6 , Br claim 6 , Me claim 6 , OCH claim 6 , and cyano.11. The compound of wherein Ris selected from the group consisting of F claim 6 , Cl claim 6 , Br claim 6 , Me claim 6 , and OCH;12. The compound of wherein Ris selected from the group consisting of F claim 6 , Cl claim 6 , Br claim 6 , CH claim 6 , CF claim 6 , OCH claim 6 , cyano claim 6 , N(CH) claim 6 , and morpholino.15. The compound of where A is COOH.17. The compound of wherein Ris H.18. The compound of wherein Ris H.19. The compound of wherein{'sub': '1', 'Ris selected from the group consisting of H and F;'}{'sub': '2b', 'Ris selected from the group consisting of H, F, and Cl;'}{'sub': '2c', 'Ris H; and'}{'sub': '4', 'Ris selected from the group consisting of H, F, Cl, and cyano.'}22. The compound of wherein A is COOH.24. The compound of wherein Ris H.25. The compound of wherein Ris H.26. The compound of wherein{'sub': 'ea', 'Ris selected from the group consisting of H, F, Cl, Br, and cyano;'}{'sub': '2b', 'Ris selected from the group ...

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Номер записи: 31
03-10-2013 дата публикации

Therapeutic Compounds for Protozoal and Microbial Infections and Cancer

Номер: US20130261133A1
Автор: Bolstad David Brian, Hoody John Howard
Принадлежит: The University of Montana

The compounds of the invention exhibit antiprotozoal, antimicrobial, and anticancer properties that are useful for the treatment or prevention of infections or cancer in a patient (e.g., a human). For example, the compounds and methods described herein can be used for the treatment or prevention of protozoal infections such as leishmaniasis, malaria, and infections, bacterial infections such as and , and cancers such as breast, colon, lung, or prostate cancer. The invention further provides methods of synthesizing such compounds as well as kits useful for administering the compounds. 2. The compound of claim 1 , wherein said compound is selected from the group consisting of (3S claim 1 ,8R)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 , ...

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Номер записи: 32
17-10-2013 дата публикации

SODIUM SALT OF 6-FLUORO-3-HYDROXY-2-PYRAZINE CARBOXAMIDE

Номер: US20130274472A1
Автор: Nakamatsu Namika, Takakura Keiko, Takeshima Sakiko, Uehara Sayuri
Принадлежит: Toyama Chemical Co., Ltd.

A preparation replete with crystals of a sodium salt of 6-fluoro-3-hydroxy-2-pyrazine carboxamide has superior solubility, and is useful as a preparation for injection. 1. A crystal of a sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or a hydrate thereof.2. An injectable preparation containing a crystal of a sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide or a hydrate thereof.3. A lyophilized preparation containing a crystal of a sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide.4. A process for producing a lyophilized preparation containing a crystal of a sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide , comprising the steps:(1) cooling an aqueous solution containing a sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide to produce a frozen product;(2) increasing the temperature of the frozen product;(3) cooling the frozen product again; and(4) carrying out lyophilization.5. The process according to claim 4 , wherein the achieving temperature of the frozen product falls within the range of −15 to −5° C. in the step of increasing the temperature of the frozen product. The present invention relates to a crystal of sodium salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide (hereinafter referred to as “Compound A”), an injectable preparation containing the same, and a process thereof.These days, worldwide pandemic has been caused by H1N1 influenza virus, and occurrence of pandemic by a further virulent virus in the future is a concern.At present, as therapeutic agents for influenza, e.g., Oseltamivir, Zanamivir, Peramivir, Laninamivir, and Amantadine are used. However, these therapeutic agents have, for example, the following drawbacks. Oseltamivir cannot be administered to patients having difficulty in oral administration. It is difficult to administer Zanamivir to children and aged persons. It takes a long time to administer Peramivir. Amantadine is ineffective against Type B influenza virus and resistant viruses have emerged. ...

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Номер записи: 33
24-10-2013 дата публикации

PROCESS FOR PRODUCING COELENTERAMIDE OR AN ANALOG THEREOF

Номер: US20130281680A1
Автор: INOUYE Satoshi
Принадлежит:

A process for producing coelenteramide or its analog in a high yield has been desired. The invention provides a process for producing di-O-methylcoelenteramide or its analog of formula (3) 120-. (canceled) The present invention relates to a process for producing coelenteramide or an analogous compound thereof, a process for producing a green fluorescent protein (gFP), and the like.A calcium-binding photoprotein is one of the proteins responsible for bioluminescence. This photoprotein instantaneously emits a flash of light upon specific interaction with Ca. The calcium-binding photoprotein is a complex of a protein having the catalytic function of oxygenation and the peroxide of a luciferin as a luminescence substrate. In the calcium-binding photoprotein, the protein having the catalytic function of oxygenation is called an apoprotein (e.g., apoaequorin). The peroxide of a luciferin is 2-hydroperoxycoelenterazine. Such known calcium-binding photoproteins are those derived from coelenterates, specifically including aequorin, clytin-I, clytin-II, mitrocomin, obelin, etc.Among them, aequorin is a photoprotein isolated from the luminous jellyfish (1: Shimomura, In: , (2006) pp 90-158, World Scientific Pub. Co.; 2: Shimomura et al., (1962) 59, pp 223-240). This aequorin is a non-covalent complex of apoaequorin (21.4 kDa) and a hydroperoxide of coelenterazine (3: Head et al., (2000) 405 372-376). Apoaequorin is a single polypeptide composed of 189 amino acid residues with 3 EF hand motifs characteristic of Ca-binding site (4: Inouye et al., (1985) 82, 3154-3158). In the presence of Ca, aequorin emits blue light (λ=˜460 nm) by an intramolecular reaction and decomposes itself into apoaequorin, coelenteramide and CO(5: Shimomura & Johnson (1972) 11, 1602-1608; 6: Shimomura & Johnson (1973) 2963-2966). The complex of Ca-bound apoaequorin with coelenteramide obtained by this decomposition is known as blue fluorescent protein (BFP) (7: Shimomura & Johnson (1975) 256, 236-238). ...

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Номер записи: 34
24-10-2013 дата публикации

METHOD FOR PREPARING ROSUVASTATIN SALTS

Номер: US20130281694A1
Автор: Barkoczy Jozsef, Bartha Ferenc Lorant, Debreczeni Jozsef, Keszthelyi Adrienn, Krasznai Gyorgy, Lukács Gyula, MILEN Mátyás, Molnár Enikö, Pandur Angéla, Pongo Laszlo, Porcs-Makkay Márta, Ruzsics György, SZABÓ Tibor, TOTHNE LAURITZ Maria, Volk Balazs
Принадлежит: EGIS GYOGYSZERGYAR NYILVANOSAN MUKODO RESZVENY-TARSASAG

The present invention is related to methods for the preparation of pharmaceutically acceptable salts of (+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3R,5S,6E)-dihydroxy-hept-6-enoic acid, intermediates thereof and methods for producing said intermediates. 5. Method according to claim 19 , which comprises using a compound of general Formula (X) wherein Ris 1-butyl or 2 claim 19 ,2-dimethyl-ethyl and Rand Rare hydrogen claim 19 , respectively.6. Method according to claim 19 , wherein for each mole of the compound of the general Formula (III) claim 19 , 1 to 30 claim 19 , preferably 20 molar equivalents of the compound of the general Formula (X) are used.7. Method according to claim 19 , characterized by that the reaction is carried out at a temperature between 80 and 140° C. claim 19 , preferably between 110 and 130° C.9. Method according to claim 8 , which comprises using a compound of the general Formula (X) claim 8 , wherein Ris 2 claim 8 ,2-dimethylethyl claim 8 , Rand Rare hydrogens.10. Method according to claim 8 , which comprises using a compound of the general Formula (X) wherein Ris 1-butyl claim 8 , Rand Rare hydrogens.12. Method according to claim 11 , characterized by that as a compound of the general Formula (X) claim 11 , the compound is used wherein Ris 2 claim 11 ,2-dimethylethyl claim 11 , Rand Rare each hydrogens.13. Method according to claim 11 , characterized by that as a compound of the general Formula (X) claim 11 , the compound wherein Ris 1-butyl claim 11 , Rand Rare each hydrogens is used.14. Crystalline Form II rosuvastatin t-butylammonium salt of the Formula (IIa) characterized by the following X-ray diffraction lines measured using CuKα radiation: (±0.2° 2Θ): 18.654 degrees 2Θ; or 18.654 and 15.803 degrees 2Θ; or 11.282 claim 11 , 15.803 and 19.832 degrees 2Θ.15. Crystalline Form II rosuvastatin t-butylammonium salt of the Formula (IIa) according to claim 14 , characterized by the following X-ray ...

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Номер записи: 35
14-11-2013 дата публикации

Fatty Amine Salts Of Herbicidal Pyrimidines

Номер: US20130303369A1
Автор: Barrientos Carlos F.
Принадлежит: E. I. DU PONT DE NEMOURS AND COMPANY

This invention is directed to () a soluble intermediate prepared from reaction of the acid form of one or more of the compounds disclosed by Formula I given below with at least one long-chain fatty amine; () a process for solubilizing one or more of the compounds disclosed by Formula I given below by reacting said compounds with at least one long-chain fatty amine to form a fatty-amine salt of Formula I compound; and () a finished pesticide product comprising at least one of the soluble intermediates, that is, fatty-amine salt of Formula I compound. 2. The process as recited in claim 1 , wherein said acid-form of at least one active ingredient compound described in Formula I is contacted with said at least one long-chain fatty amine under high shear condition.3. The process as recited in claim 2 , wherein:{'sup': 2', '12', '13', '46', '47', '14', '48', '49', '15', '16', '17', '18', '19', '50', '51', '52', '53', '54, 'sub': 2', '2', '2', 'y, 'Ris COR, CHOR, CH(OR)(OR), CHO, C(═NOR)H, C(═NNRR)H, (O)C(R)(R)COR, C(═O)N(R)R, C(═S)OR, C(═O)SR, C(═S)SRor C(═NR)R;'}{'sup': 12', '55', '56', '27, 'sub': 2', 'm', '1', '14', '3', '12', '4', '12', '4', '12', '2', '14', '2', '14, 'Ris H, —CH\ue8a0C(O)O(CH)\ue8a0, —N═C(R)R; or a radical selected from C-Calkyl, C-Ccycloalkyl, C-Calkylcycloalkyl, C-Ccycloalkylalkyl, C-Calkenyl, C-Calkynyl and phenyl, each radical optionally substituted with 1-3 R; or'}{'sup': 12', '12, 'sub': 2', '2', '2', '2', '2', '3', '3', '2, 'Ris a divalent radical linking the carboxylic ester function CORof each of two pyrimidine ring systems of Formula I, the divalent radical selected from —CH—, —(CH)—, (CH)— and —CH(CH)CH—;'}{'sup': 13', '28, 'sub': 1', '10, 'Ris H, C-Calkyl optionally substituted with 1-3 R, or benzyl;'}{'sup': '14', 'sub': 1', '4', '1', '4, 'Ris H, C-Calkyl, C-Chaloalkyl or benzyl;'}{'sup': 17', '29, 'sub': 1', '10, 'Ris C-Calkyl optionally substituted with 1-3 R, or benzyl;'}{'sup': 18', '57, 'sub': 1', '4', '2, 'Ris H, C-Calkyl, hydroxy, ...

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Номер записи: 36
14-11-2013 дата публикации

HCV Protease Inhibitors and Uses Thereof

Номер: US20130303547A1
Автор: Anderson David D., Bosse Todd D., Chen Hui-Ju, Cooper Curt S., Green Brian E., Klein Larry L., Krueger Allan C., Larson Daniel P., Liu Dachun, McDaniel Keith F., MOTTER Christopher E., Pratt John K., Rockway Todd W., Rosenberg Teresa A., Shanley Jason P., Yeung Ming C.
Принадлежит:

This invention relates to: (a) compounds of formula I and salts thereof that, inter alia, are useful as hepatitis C virus (HCV) inhibitors; (b) intermediates useful for the preparation of such compounds and salts; (c) pharmaceutical compositions comprising such compounds and salts; and (d) methods of use of such compounds, salts, and compositions. 3. The compound or salt of claim 1 , wherein each Ris independently selected from the group consisting of carbocyclyl claim 1 , heterocyclyl claim 1 , alkylcarbonyl claim 1 , alkenylcarbonyl claim 1 , alkynylcarbonyl claim 1 , alkyloxycarbonyl claim 1 , alkenyloxycarbonyl claim 1 , alkynyloxycarbonyl claim 1 , carbocyclylcarbonyl claim 1 , heterocyclylcarbonyl claim 1 , carbocyclyloxycarbonyl claim 1 , heterocyclyloxycarbonyl claim 1 , aminoalkylcarbonyl claim 1 , carbocyclylaminocarbonyl claim 1 , heterocyclylaminocarbonyl claim 1 , carbocyclylalkyloxycarbonyl claim 1 , heterocyclylalkyoxycarbonyl claim 1 , alkylcarbocyclylsulfonyl claim 1 , and alkylheterocyclylsulfonyl claim 1 , wherein:the amino portion of the aminoalkylcarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyloxycarbonyl, carbocyclylalkyloxycarbonyl, and heterocyclylalkyloxycarbonyl.4. The compound or salt of claim 1 , wherein each Ris independently selected from the group consisting of carbocyclyl claim 1 , heterocyclyl claim 1 , alkylcarbonyl claim 1 , alkyloxycarbonyl claim 1 , carbocyclylcarbonyl claim 1 , carbocyclyloxycarbonyl claim 1 , aminoalkylcarbonyl claim 1 , heterocyclylaminocarbonyl claim 1 , carbocyclylalkyloxycarbonyl claim 1 , and alkylcarbocyclylsulfonyl claim 1 , wherein:the amino portion of the aminoalkylcarbonyl optionally is substituted with one or two independently selected carbocyclylalkyloxycarbonyl.5. The compound or salt of claim 1 , wherein:{'sup': 8', 'B, 'Ris aminocarbonyl substituted with R; and'}{'sup': 'B', 'claim-text': the amino portion of the ...

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Номер записи: 37
28-11-2013 дата публикации

PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES

Номер: US20130317066A1
Автор: Flynn Daniel L., Kaufman Michael D.
Принадлежит: DECIPHERA PHARMACEUTICALS, INC.

Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. 5. The compound of claim 4 , wherein R3 is C1-C6 alkyl claim 4 , C3-C8 branched alkyl claim 4 , C3-C8 cycloalkyl or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , enantiomer stereoisomer or tautomer thereof.6. The compound of claim 4 , wherein R3 is —NR6(R7) or R4 claim 4 , or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , enantiomer stereoisomer or tautomer thereof.76. A compound of any one of - wherein R1 is fluoro or H and n is 1.817. A compound of claims any one of - wherein R2 is C1-C6 alkyl or C3-C8 branched alkyl.12. The compound of claim 11 , wherein R3 is C1-C6 alkyl claim 11 , C3-C8 branched alkyl claim 11 , C3-C8 cycloalkyl or a pharmaceutically acceptable salt claim 11 , hydrate claim 11 , solvate claim 11 , enantiomer stereoisomer or tautomer thereof.13. The compound of claim 11 , wherein R3 is —NR6(R7) or R4 or a pharmaceutically acceptable salt claim 11 , hydrate claim 11 , solvate claim 11 , enantiomer stereoisomer or tautomer thereof.1413. A compound of any one of - wherein R1 is fluoro or H and n is 1.15914. A compound of claims any one of - wherein R2 is C1-C6 alkyl or C3-C8 branched alkyl.16. A compound selected from the group consisting of N-(4-((2-acetamidopyridin-4-yl)oxy)-2 claims 9 ,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(2 claims 9 ,5-difluoro-4-((2-propionamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2 claims 9 ,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide claims 9 , N-(2 claims 9 ,5-difluoro-4-((2-pivalamidopyridin-4-yl)oxy)phenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1 claims 9 ,2-dihydropyridine-3-carboxamide ...

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Номер записи: 38
12-12-2013 дата публикации

INHIBITORS OF PROTEIN KINASES

Номер: US20130331407A1
Автор: Allgeier Hans, Augustin Martin, Peraus Gisela, Pleiss Michael A., Schauerte Heike, Stumm Gabriele, Wabnitz Philipp
Принадлежит: Ingenium Pharmaceuticals GmbH

The present invention relates to inhibitors of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to methods of preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases comprising the administration of an effective amount of at least one inhibitor of cyclin-dependent kinases. 2. The method of claim 1 , wherein the pain comprises chronic pain claim 1 , inflammatory pain claim 1 , neuropathic pain claim 1 , or a combination thereof.3. A method for treatment of a disease selected from the group of pain claim 1 , an inflammatory disorder claim 1 , an immunological disease claim 1 , a proliferative disease claim 1 , an infectious disease claim 1 , a cardiovascular disease and a neurodegenerative disease claim 1 , comprising administering a therapeutically effective amount of at least one compound represented by general Formula I wherein Ris 1 to 3 substituents independently selected from the group consisting of methyl claim 1 , ethyl claim 1 , hydroxymethyl claim 1 , hydroxy claim 1 , methoxy claim 1 , ethoxy claim 1 , isopropoxy claim 1 , benzyloxy claim 1 , hydrogen claim 1 , fluoro claim 1 , chloro claim 1 , trifluoromethyl claim 1 , 2-methoxy-ethoxy claim 1 , methoxymethyl claim 1 , 2-methoxy-ethyl claim 1 ,{'sub': 3', '2', '3, 'tetrahydro-furan-3-yloxy, tetrahydro-furan-2-yl-methoxy, —N(CH)SOCH, piperidin-1-yl-methyl, 2-hydroxymethyl-piperidin-1-yl-methyl, 3-hydroxymethyl-piperidin-1-yl-methyl, 3-(2-hydroxy-ethyl)-piperidin-1-yl-methyl, 3-aminocarbonyl-piperidin-1-yl-methyl, dimethylaminomethyl, diethylaminomethyl, (ethyl-isopropyl-amino)-methyl, morpholin-4-ylmethyl, 4-methyl-piperazin-1-yl-methyl, [1,2,4]triazol-1-yl-methyl, pyridine-3-yl-methoxy, and pyridine-4-yl-methoxy to a patient suffering from said disease.'}4. The method of claim 3 , wherein the pain comprises chronic pain ...

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Номер записи: 39
19-12-2013 дата публикации

Compounds and methods for inhibiting phosphate transport

Номер: US20130336918A1
Автор: Christopher Carreras, Dominique Charmot, Eric Labonte, Han-Ting Chang, Jason G. Lewis, Jeffrey W. Jacobs, Marc Navre, Michael R. Leadbetter, Nicholas Reich, Noah Bell, Tao Chen
Принадлежит: Ardelyx Inc

Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

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Номер записи: 40
19-12-2013 дата публикации

Chemosensory Receptor Ligand-Based Therapies

Номер: US20130338095A1
Автор: Baron Alain D., Beeley Nigel R.A., Brown Martin R., Jones Christopher R.G.
Принадлежит: Elcelyx Therapeutics, Inc.

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administering a composition comprising a chemosensory receptor ligand. Also provided herein are chemosensory receptor ligand compositions and methods for the preparation thereof for use in the methods of the present invention. 193-. (canceled)120. A composition according to claim 94 , wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.121. A composition according to claim 94 , wherein one or more regions of the intestine are the duodenum claim 94 , jejunum claim 94 , ileum claim 94 , caecum claim 94 , colon and/or rectum.122. A composition according to claim 94 , wherein the composition releases at an onset of about 5 to about 45 minutes claim 94 , about 105 to about 135 minutes claim 94 , about 165 to about 195 minutes claim 94 , about 225 to about 255 minutes or a combination of times thereof following administration to a subject.123. A composition according to claim 94 , wherein the composition releases at an onset of about pH 5.0 claim 94 , about pH 5.5 claim 94 , about pH 6.0 claim 94 , about pH 6.5 claim 94 , about pH 7.0 claim 94 , or combination thereof following administration to a subject.124. A composition according to claim 94 , the composition further comprising a second chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand claim 94 , a bitter receptor ligand claim 94 , an umami receptor ligand claim 94 , a fat receptor ligand claim 94 , a sour receptor ligand and a bile acid receptor ligand.125. A composition according to claim 124 , wherein the sweet receptor ligand is selected from the group consisting of sucralose claim 124 , aspartame claim 124 , Stevioside claim 124 , Rebaudioside A claim 124 , Rebaudioside B claim 124 , Rebaudioside C claim 124 , Rebaudioside D claim 124 , ...

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Номер записи: 41
19-12-2013 дата публикации

METHOD FOR THE PREPARATION OF HIGH-PURITY PHARMACEUTICAL INTERMEDIATES

Номер: US20130338360A1
Автор: Bagyinszki Gabor, Barkoczy Jozsef, Bartha Ferenc Lorant, Imre Janos, Keszthelyi Adrienn, Kovanyine Lax Gyorgyi, Krasznai Gyorgy, Morovjan Gyorgy, Nagy Kalman, Ruzsics György, Simig Gyula, Sipos Eva, Volk Balazs
Принадлежит: EGIS Gyogyszergyar Nyilvanosan Mukodo Reszvenytars

The present invention is related to intermediates useful in the preparation of pharmaceutically acceptable salts of (+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3R,5S)-dihydroxy-hept-6-enoic acid and polymorphs of said intermediates, methods for preparation thereof and use thereof. 3. A method according to claim 1 , which is a method III for the preparation of amorphous rosuvastatin TBA salt of the Formula (III) claim 1 , which comprises dissolving rosuvastatin TBA salt in a saturated aliphatic alcohol having one to four carbon atoms claim 1 , preferably in methanol claim 1 , removing the solvent and drying the solid residue at room temperature in air.5. Crystalline Form II rosuvastatin TBA salt of the Formula (III) according to claim 4 , having the X-ray diffraction signals measured with CuK radiation exceeding 50% relative intensity during powder X-ray diffraction analysis: 15.803 and 18.651 degrees (+/−0.2°) (2Θ).6. Crystalline Form II rosuvastatin TBA salt of the Formula (III) according to claim 4 , having the X-ray diffraction signals measured with CuK radiation exceeding 25% relative intensity during powder X-ray diffraction analysis at 11.282 claim 4 , 15.803 claim 4 , 18.651 claim 4 , 19.050 claim 4 , 19.832 and 20.512 degrees (+/−0.2°) (2Θ).8. Amorphous rosuvastatin TBA salt according to .10. A method for preparing a rosuvastatin calcium (2:1) salt claim 1 , which includes a reaction involving a rosuvastatin TBA salt of Formula (III) prepared according to claim 1 , which method is one of the methods I to III.11. A method for preparing a rosuvastatin zinc (2:1) salt claim 1 , which includes a reaction involving a rosuvastatin TBA salt of Formula (III) prepared according to claim 1 , which method is one of the methods I to III.12. Crystalline Form II rosuvastatin methylester of the Formula (IIa) according to claim 4 , having the most intense diffraction signals measured in powder X-ray diffractometry using CuK ...

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Номер записи: 42
02-01-2014 дата публикации

PROCESSES AND INTERMEDIATES FOR CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS

Номер: US20140005405A1
Автор: DUAN Maosheng, HAKOGI Toshikazu, JOHNS Brian
Принадлежит:

Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent. In particular, a compound of formula (I) can be produced from (II) and avoid the use of an allyl amine: (formulae I and II) where R, PP, Rand Rare as described herein. 122-. (canceled)24. The process of claim 23 , wherein in said compound of formula (I) claim 23 , R is —CHO.25. The process of claim 23 , wherein in said compound of formula (I) claim 23 , R is —CH(OH)(OR).30. The process according to wherein in said compound of formula (I) claim 23 , Ris H claim 23 , halogen claim 23 , hydroxy claim 23 , optionally substituted lower alkyl claim 23 , optionally substituted cycloalkyl claim 23 , optionally substituted lower alkenyl claim 23 , or optionally substituted lower alkoxy.32. The process of claim 23 , wherein said refunctionalizing step ii) comprises demethylating the intermediate of formula (V) to produce the compound of formula (I).33. The process of claim 23 , wherein said refunctionalizing step ii) comprises reacting the intermediate of formula (VI) with NaIOto produce the compound of formula (I).34. The process of claim 23 , wherein Ris H. The present invention comprises modifications of known processes for synthesizing compounds having HIV integrase inhibitory activity.WO 2006/116764 published 2 Nov. 2006, incorporated by reference in its entirety, describes various compounds and detailed synthetic schemes for their preparation. In particular, the 16, 27and 32steps involve the creation of a —CHO group from a double bond using a reagent which may include osmium tetroxide.Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent.The present invention ...

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Номер записи: 43
30-01-2014 дата публикации

POLY AROMATIC SODIUM CHANNEL BLOCKERS

Номер: US20140031371A1
Автор: JOHNSON Michael Ross
Принадлежит: PARION SCIENCES, INC.

Polyaromatic sodium channel blockers represented by the formula: 147-. (canceled)50. The method of claim 48 , wherein Ais selected from indenyl claim 48 , napthalenyl claim 48 , 1 claim 48 ,2-dihydronapthalenyl claim 48 , 1 claim 48 ,2 claim 48 ,3 claim 48 ,4-tetrahydronapthalenyl claim 48 , anthracenyl claim 48 , fluorenyl claim 48 , phenanthrenyl claim 48 , azulenyl claim 48 , cyclohepta-1 claim 48 ,3 claim 48 ,5-trienyl or 5H-dibenzo[a claim 48 ,d]cycloheptenyl claim 48 , substituted with at least one Rand the remaining substituents are R.51. The method of claim 48 , wherein Ris hydrogen and Ris a group represented by formula A.53. The method of claim 52 , wherein one Q is C—Rand the remaining Q are C—H.55. The method of claim 48 , wherein Ris Link-(CH)—CAP.56. The method of claim 48 , wherein Ris Link-(CH)—(Z)—CAP.57. The method of claim 48 , wherein Ris Link-(CH)(Z)—(CH)—CAP.58. The method of claim 48 , wherein Ris —(CH)—NR—CH(CHOR)(CHOR)—CHOR.59. The method of claim 48 , wherein Ris —O—(CH)—NR—CH(CHOR)(CHOR)—CHOR.60. The method of claim 48 , wherein CAP is —(Z)R.61. The method of claim 48 , wherein CAP is —CR((Z)R)((Z)R).62. The method of claim 48 , wherein the compound of formula (I) is an acid addition salt of an acid selected from the consisting of hydrochloric acid claim 48 , hydrobromic acid claim 48 , sulfuric acid claim 48 , phosphoric acid claim 48 , nitric acid claim 48 , acetic acid claim 48 , oxalic acid claim 48 , tartaric acid claim 48 , succinic acid claim 48 , maleic acid claim 48 , fumaric acid claim 48 , gluconic acid claim 48 , citric acid claim 48 , malic acid claim 48 , ascorbic acid claim 48 , benzoic acid claim 48 , tannic acid claim 48 , palmitic acid claim 48 , alginic acid claim 48 , polyglutamic acid claim 48 , naphthalensulfonic acid claim 48 , methanesulfonic acid claim 48 , p-toluenesulfonic acid claim 48 , naphthalenedisulfonic acid claim 48 , polygalacturonic acid claim 48 , malonic acid claim 48 , sulfosalicylic acid claim 48 , ...

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Номер записи: 44
06-02-2014 дата публикации

SULFONYL-DERIVATIVES AS NOVEL INHIBITORS OF HISTONE DEACETYLASE

Номер: US20140038979A1
Автор: Arts Janine, Backx Leo-Jacobus Jozef, De Winter Hans Louis Jos, Dyatkin Alexey Borisovich, Meerpoel Lieven, Pilatte Isabelle Noëlle Constance, Poncelet Virginie Sophie, Van Brandt Sven Franciscus Anna, Van Emelen Kristof, Van heusden Jimmy Arnold Viviene, Verdonck Marc Gustaaf Celine
Принадлежит: Janssen Pharmaceutica NV

This invention comprises the novel compounds of formula (I) 4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound of .10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. A method of detecting or identifying a HDAC in a biological sample comprising detecting or measuring the formation of a complex between a labelled compound as defined in and a HDAC.15. A combination of one or more anti-cancer agent and a a compound of .18. The compound of claim 1 , wherein -L- is a direct bond or a bivalent radical selected from Calkanediyl claim 1 , carbonyl and aminocarbonyl.19. The compound of claim 18 , wherein -L- is a direct bond claim 18 , —C(O)— claim 18 , or methyl.20. The compound of claim 19 , wherein -L- is a direct bond.21. The compound of claim 1 , wherein Ris selected from hydrogen claim 1 , halogen claim 1 , Calkyl claim 1 , —C(O)NRR; and{'sup': '2', 'sub': 1-6', '1-6, 'Ris hydrogen, halo, hydroxy, nitro, Calkyl, Calkyloxy, trifluoromethyl, or hydroxyamino.'}22. The compound of claim 1 , wherein Ris selected from hydrogen; nitro; trihaloCalkyl; trihaloCalkyloxy; Calkyl; Calkyloxy; Calkylcarbonyl; aryloxy; di(Calkyl)amino; C(O)NHOH; NHC(O)CHNH claim 1 , C(O)NHCHCHOH claim 1 , NHC(O)NHOH claim 1 , and NHC(O)CH. This invention concerns compounds having histone deacetylase (HDAC) inhibiting enzymatic activity. It further relates to processes for their preparation, to compositions comprising them, as well as their use, both in vitro and in vivo, to inhibit HDAC and as a medicine, for instance as a medicine to inhibit proliferative conditions, such as cancer and psoriasis.In all eukaryotic cells, genomic DNA in chromatine associates with histones to form nucleosomes. Each nucleosome consists of a protein octamer made up of two copies of each histones H2A, H2B, H3 and H4. DNA winds around this protein ...

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Номер записи: 45
06-02-2014 дата публикации

CXCR4 ANTAGONISTS FOR THE TREATMENT OF MEDICAL DISORDERS

Номер: US20140039187A1
Автор: Liang Zhongxing, Liotta Dennis C., Shim Hyunsuk, Snyder James P., Zhan Weiqiang
Принадлежит:

The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis. 2. The method of claim 1 , wherein the reducing agent is sodium triacetoxyborohydride.4. The method of claim 3 , wherein the carboxylic acid is tartaric acid. This application claims priority to U.S. Provisional Application No. 60/642,375, filed Jan. 7, 2005 and U.S. Provisional Application No. 60/642,374, filed Jan. 7, 2005.The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor. The compounds are useful to mediate any medical condition that is modulated by CXCR4 receptor signaling, and in particular for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.Cancer is currently the second leading cause of death in developed nations. In 2004, the American Cancer Society estimated that approximately 1.37 million new cases were diagnosed in the U.S. alone, and approximately 550,000 deaths occurred due to cancer (American Cancer Society, Cancer Facts & Figures 2004, see URL: http://www.cancer.org/docroot/STT/stt0.asp).Metastasis, the spread and growth of tumor cells to distant organs, is the most devastating attribute of cancer. Most morbidity and mortality associated with certain types of cancer, such as breast cancer, is associated with disease caused by metastatic cells rather than by the primary tumor. Therapy for metastasis currently relies on a combination of early diagnosis and aggressive treatment of the primary tumor.The establishment and growth of metastases at distant sites is thought to depend ...

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Номер записи: 46
06-02-2014 дата публикации

Fluorescent Pyrazine Derivatives and Methods of Using the Same in Assessing Renal Function

Номер: US20140039191A1
Автор: Dorshow Richard B., Moore Dennis A., Neumann William L., Rajagopalan Raghavan
Принадлежит: MediBeacon, LLC

The present invention relates to pyrazine derivatives such as those represented by Formulas I and II. Xto Xof Formulas I and II may be characterized as electron withdrawing groups, while Yto Yof Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing organ (e.g., kidney) function. In a particular example, an effective amount of a pyrazine derivative that is capable of being renally cleared may be administered into a patient's body. The pyrazine derivative may capable of one or both absorbing and emanating spectral energy of at least about 400 nm (e.g., visible and/or infrared light). At least some of the derivative that is in the body may be exposed to spectral energy and, in turn, spectral energy may emanate from the derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient. 4. The compound of wherein:{'sup': 1', '2', '12', '13, 'each of Yand Yis —NRR; and'}{'sup': 12', '13, 'sub': 2', 'a', '2, 'each of Rand Ris —(CH)COH.'}7. The compound of wherein:{'sup': 1', '2', '12', '13, 'each of Yand Yis —NRR; and'}{'sup': 12', '13, 'sub': 2', 'a', '2, 'each of Rand Ris —(CH)COH.'}11. The compound of wherein:{'sup': 3', '4, 'each of Xand Xis —CN;'}{'sup': 2', '37', '38, 'sub': '2', 'Zis selected from the group consisting of a direct bond, —O—, —NR—, —NCOR—, —S—, —SO— and —SO—;'}{'sup': 31', '32', '40', '−, 'sub': 2', '2', '2', '2', 'b', '2', 'b', '2', 'b', '2', '2', 'b', '3', '2', 'b', '3, 'each of Rand Ris independently selected from the group consisting of C3-C6 polyhydroxylated alkyl, —((CH)—O—(CH)—O)—R, —(CH)OH, —(CH)COH, —(CH)SOH and —(CH)SO; and'}{'sup': 37', '38', '40', '−, 'sub': 2', '2', '2', '2', 'b', '2', 'b', '2', 'b', '2', '2', 'b', '3', '2', 'b', '3, 'each of Rand Ris independently selected from the group consisting of hydrogen, C3-C6 polyhydroxylated alkyl, —((CH)—O—(CH)—O)—R, C1-C10 alkyl, —(CH)OH, —(CH)COH, —(CH)SOH ...

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Номер записи: 47
06-03-2014 дата публикации

Analysis of amino acid copolymer compositions

Номер: US20140065652A1
Автор: Corinne Bauer, James Eric Anderson, Peter James Ahern, Xiangping Zhu, Yanjie Jiang, Zachary Shriver
Принадлежит: Momenta Pharmaceuticals Inc

Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard.

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Номер записи: 48
13-03-2014 дата публикации

Biological Buffers with Wide Buffering Ranges

Номер: US20140073789A1
Автор: Daly Thomas
Принадлежит:

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability. 2. The surfactant of where A=D=—CH claim 1 , E=—CHOH claim 1 , Q=—CHP(OH)O.3. The surfactant of where A=D=E=—CHOH claim 1 , Q=—CHP(OH)O.4. The surfactant of where A=D=E=—CH claim 1 , Q=—CHCOOJ claim 1 , J=—H.5. The surfactant of where A=D=—CH claim 1 , E=—H claim 1 , Q=—CHCOOJ claim 1 , J=—H.6. The surfactant of where A=D=—CH claim 1 , E=—CHOH claim 1 , Q=—CHCOOJ claim 1 , J=—H.7. The surfactant of where A=D=E=—CHOH claim 1 , Q=—CHCOOJ claim 1 , J=—H.8. The surfactant of where A=D=—CH claim 1 , E=—CHOH claim 1 , Q=—CHCHSOH.9. The surfactant of where A=D=E=—CHOH claim 1 , Q=—CHCHSOH.12. The biological buffer of where A=D=—CH claim 11 , E=—CHOH claim 11 , G=—CH claim 11 , Q=—CHP(OH)O.13. The biological buffer of where A=D=—CH claim 11 , E=—CHOH claim 11 , G=—H claim 11 , Q=—CHP(OH)O.14. The biological buffer of where A=D=E=—CHOH claim 11 , G=—CH claim 11 , Q=—CHP(OH)O.15. The biological buffer of where A=D=E=—CHOH claim 11 , G=—H claim 11 , Q=—CHP(OH)O.16. The biological buffer of where A=D=—CH claim 11 , E=—CHOH claim 11 , Q=—CHCHSOH.17. The biological buffer of where A=D=E=—CHOH claim 11 , Q=—CHCHSOH.18. The biological buffer of where A=D=E=—CHOH claim 11 , Q=—CHCH(CH)COOJ and J=—H.19. The biological buffer of where A=D=—CH claim 11 , E=—CHOH claim 11 , Q=—CHCH(CH)COOJ and J=—H. This application is a continuation in part of application Ser. No. 13/588,530 filed Aug. 17, 2012 which was a continuation in part of application Ser. No. 13/267,440 filed Oct. 6, 2011 which was a ...

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Номер записи: 49
10-04-2014 дата публикации

SULFONYL AMIDE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH

Номер: US20140100368A1
Автор: Autry Christopher Lowell, Bhattacharya Samit Kumar, Freeman-Cook Kevin Daniel, Hayward Matthew Merrill, Hulford Catherine Angela, Luzzio Michael Joseph, Nelson Kendra Louise, Xiao Jun, Zhao Xumiao
Принадлежит:

The present invention relates to a compound of the formula I 120-. (canceled)22. The method of claim 21 , wherein the reaction is performed in the presence of a catalyst.23. The method of claim 22 , wherein the catalyst is 10% palladium on carbon.24. The method of claim 21 , wherein the reaction is performed in the presence of a solvent.25. The method of claim 24 , wherein the solvent is 2N methanolic NH.26. The method of claim 21 , wherein the reaction of the compound of Formula (B1) with hydrogen is performed under hydrogen pressure.27. The method of claim 26 , wherein the pressure is 45 psi.28. The method of claim 21 , wherein the reaction is performed in a Parr reactor.29. The method of claim 21 , wherein the reaction is performed at ambient temperature.30. The method of claim 29 , wherein the temperature is 25° C.31. The method of claim 21 , wherein the reaction is performed for 3 hours.32. The method of claim 21 , further comprising isolating the compound of Formula (B2) claim 21 , wherein isolating the compound of Formula (B2) comprises filtration.33. The method of claim 32 , wherein the filtration is through Celite.35. The method of claim 34 , wherein the reaction is performed in the presence of a solvent.36. The method of claim 35 , wherein the solvent is acetonitrile.37. The method of claim 34 , wherein the reaction is performed in the presence of a base.38. The method of claim 37 , wherein the base is cesium carbonate.39. The method of claim 36 , wherein the reaction is added at ambient temperature.40. The method of claim 39 , wherein the temperature is 25° C.41. The method of claim 34 , wherein the reaction is performed at elevated temperature.42. The method of claim 41 , wherein the temperature is 80° C.43. The method of claim 34 , further comprising isolating the compound of Formula (B1) claim 34 , wherein isolating the compound of Formula (B1) comprises decreasing the temperature of the reaction mixture to ambient temperature.44. The method of claim ...

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Номер записи: 50
06-01-2022 дата публикации

TREATMENT OF PULMONARY ARTERIAL HYPERTENSION USING THERAPEUTICALLY EFFECTIVE ORAL DOSES OF 10-NITRO-9(E)-OCTADEC-9-ENOIC ACID

Номер: US20220000824A1
Автор: JORKASKY Diane
Принадлежит:

Various embodiments of this invention are directed to pharmaceutical compositions and methods for treating diseases, including focal segmental glomerulosclerosis or pulmonary arterial hypertension. The compositions of such embodiments include activated fatty acids such as alkyl substituted fatty acids, keto fatty acids and nitro fatty acids. The methods of various embodiments include administering an effective amount of 10-nitro-9(E)-octadec-9-enoic acid to treat such diseases. 1. A method of treating sickle cell disease in a subject in need thereof , comprising:a. administering to said subject a daily dose of 10-nitro-9(E)-octadec-9-enoic acid in an amount of at least 25 milligrams (mg).2. The method of claim 1 , wherein said daily dose is administered orally.3. The method of claim 1 , wherein said daily dose is at least 120 mg.4. The method of claim 1 , wherein said daily dose is no more than 450 mg.5. The method of claim 1 , wherein said daily dose is divided into two doses per day.6. The method of claim 1 , wherein said two doses per day are of equal weight.7. A method of treating sickle cell disease in a subject in need thereof claim 1 , comprising:a. administering to said subject at least 25 milligrams (mg) of 10-nitro-9(E)-octadec-9-enoic acid.8. The method of claim 1 , wherein said 10-nitro-9(E)-octadec-9-enoic acid is administered orally.9. The method of claim 1 , wherein at least 50 mg claim 1 , 100 mg claim 1 , 150 mg claim 1 , 200 mg claim 1 , 250 mg claim 1 , or 300 mg of said 10-nitro-9(E)-octadec-9-enoic acid is administered.10. The method of claim 9 , wherein said 10-nitro-9(E)-octadec-9-enoic acid is administered once daily.11. The method of claim 9 , wherein said 10-nitro-9(E)-octadec-9-enoic acid is administered twice daily.12. The method of claim 9 , wherein said 10-nitro-9(E)-octadec-9-enoic acid is administered three times daily.13. The method of claim 9 , wherein said 10-nitro-9(E)-octadec-9-enoic acid is administered four times daily. The ...

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Номер записи: 51
07-01-2016 дата публикации

CXCR4 Antagonists for the Treatment of Medical Disorders

Номер: US20160002174A1
Автор: Liang Zhongxing, Liotta Dennis C., Shim Hyunsuk, Snyder James P., Zhan Weiqiang
Принадлежит:

The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis. 2. The method of claim 1 , wherein the reducing agent is sodium triacetoxyborohydride.4. The method of claim 3 , wherein the carboxylic acid is tartaric acid. This application claims priority to U.S. Provisional Application No. 60/642,375, filed Jan. 7, 2005 and U.S. Provisional Application No. 60/642,374, filed Jan. 7, 2005.The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor. The compounds are useful to mediate any medical condition that is modulated by CXCR4 receptor signaling, and in particular for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.Cancer is currently the second leading cause of death in developed nations. In 2004, the American Cancer Society estimated that approximately 1.37 million new cases were diagnosed in the U.S. alone, and approximately 550,000 deaths occurred due to cancer (American Cancer Society, Cancer Facts & Figures. 2004, see URL: http://www.cancer.org/docroot/STT/stt0.asp).Metastasis, the spread and growth of tumor cells to distant organs, is the most devastating attribute of cancer. Most morbidity and mortality associated with certain types of cancer, such as breast cancer, is associated with disease caused by metastatic cells rather than by the primary tumor. Therapy for metastasis currently relies on a combination of early diagnosis and aggressive treatment of the primary tumor.The establishment and growth of metastases at distant sites is thought to depend ...

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Номер записи: 52
07-01-2016 дата публикации

AMIDE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS INSECTICIDE

Номер: US20160002198A1
Автор: Banba Shinichi, CHIBA Yutaka, Daido Hidenori, Kai Akiyoshi, Kato Hiroko, Katsuta Hiroyuki, Kawahara Nobuyuki, Maki Junji, Nomura Michikazu, TAKAHASHI Kiyoshi, Wakita Takeo, YOSHIDA Kei
Принадлежит:

An object of the present invention is to provide a compound represented by Formula (1): 114-. (canceled) The present invention relates to a compound represented by Formula (1):wherein A, A, Aand Aeach represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom;Rand Reach represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group;Gand Geach represent an oxygen atom or a sulfur atom;X, which may be identical or different, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group;n is an integer of 0 to 4; andQand Qeach represent an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group,an insecticide comprising the compound as the active ingredient, and a process for preparation thereof and use thereof.International Publication WO 2000/55120 and U.S. Pat. No. 6,548,514 describe a compound similar to the compound of the present invention for the use as medicament, but they do not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.International Publication WO 2000/7980 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.US Patent Laid-Open No. 2002-032238 describes a compound similar to the compound of the present invention for the use as medicament, but it does not describe on the insecticidal activity of the compound. The compound clearly does not fall within the scope of claims of the present invention.The object of the present invention is to provide a pesticide having a high insecticidal efficacy. Another object of the present invention is to provide a compound represented by Formula (1), a process for ...

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Номер записи: 53
05-01-2017 дата публикации

CRYSTALLINE FORMS OF A HISTONE DEACETYLASE INHIBITOR

Номер: US20170001965A1
Автор: Liu Gui, SEYEDI Farzaneh, van Duzer John H.
Принадлежит:

This disclosure provides solid forms of 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, and methods of manufacturing and using these forms. 1. A crystalline form of 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide.2. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 8.3±0.2° claim 1 , 10.6±0.2° claim 1 , 16.6±0.2° claim 1 , 21.3±0.2° claim 1 , and 25.0±0.2° (Form I).3. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 11.6±0.2° claim 1 , 19.5±0.2° claim 1 , 20.2±0.2° claim 1 , 23.3±0.2° claim 1 , and 23.8±0.2° (Form II).4. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 8.3±0.2° claim 1 , 11.7±0.2° claim 1 , 13.5±0.2° claim 1 , 13.7±0.2° claim 1 , and 23.6±0.2° (Form III).5. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 11.8±0.2° claim 1 , 13.6±0.2° claim 1 , 13.8±0.2° claim 1 , 23.7±0.2° claim 1 , and 30.6±0.2° (Form IV).6. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 7.6±0.2° claim 1 , 15.1±0.2° claim 1 , 21.1±0.2° claim 1 , and 24.8±0.2° (Form V).7. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 8.2±0.2° claim 1 , 20.0±0.2° claim 1 , 22.2±0.2° claim 1 , and 24.9±0.2° (Form VI).8. The crystalline form of claim 1 , wherein the crystalline form is ...

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Номер записи: 54
12-01-2017 дата публикации

THERAPEUTIC COMPOUNDS

Номер: US20170008859A1
Автор: JURUTKA Peter, MARSHALL Pamela, WAGNER Carl
Принадлежит: Arizona Board of Regents on behalf of Arizona State University

The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia. 5. The compound of which is a compound of formula IV claim 1 , wherein Ris ethyl or isopropyl; or a salt thereof.11. A pharmaceutical composition comprising a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.12. A method for treating Alzheimer's disease claim 1 , Parkinson's disease claim 1 , diabetes claim 1 , cancer claim 1 , or a psychotic disorder in an animal comprising administering a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , to the animal.1314-. (canceled) This invention was made with government support under R15 CA139364 awarded by the National Institutes of Health. The government has certain rights in the invention.The human retinoid X receptors (hRXRs) consist of three identified isoforms (α, β, γ) that function as transcription promoters often in partnership with other members of a larger nuclear receptor (NR) family of transcription regulators including the thyroid receptor (TR), the vitamin D receptor (VDR), the liver X receptor (LXR), the peroxisome proliferator-activated receptor (PPAR), and the retinoic acid receptor (RAR). While 9-cis-retinoic acid (9-cis-RA) and docosahexaenoic acid (DHA) have been shown to bind to hRXRs and promote RXR element (RXRE) regulated transcription (i.e. function as RXR agonists), it is still unclear if RXR has a bona fide endogenous molecular ligand. RXR has been described as the central NR regulator, because it often plays a critical role, either as a permissive or non-permissive partner, in heterodimer complexes that must be formed with the other NRs to regulate their respective response elements.Recent studies have identified several RXR-selective-binding molecular ligands (rexinoids) that can modulate ...

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Номер записи: 55
14-01-2016 дата публикации

PYRAZINE GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Номер: US20160009662A1
Автор: Huang Hui, Meegalla Sanath, Player Mark R.
Принадлежит:

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I) as follows: 2. The compound of wherein Ris selected from the group consisting of phenyl and pyridin-4-yl; wherein Ris independently substituted with one or two substituents that are methoxy and fluoro; provided that phenyl of Ris substituted with no more than one methoxy substituent.3. The compound of wherein Ris 2-fluoro-5-methoxyphenyl or 5-fluoro-2-methoxypyridin-4-yl.6. The compound of wherein Ris Ccycloalkyl.7. The compound of wherein Ris cyclopropyl.13. A pharmaceutical composition comprising a compound of or and at least one of a pharmaceutically acceptable carrier claim 6 , a pharmaceutically acceptable excipient claim 6 , and a pharmaceutically acceptable diluent.14. The pharmaceutical composition of claim 13 , wherein the composition is a solid oral dosage form.15. The pharmaceutical composition of claim 13 , wherein the composition is a syrup claim 13 , an elixir or a suspension.16. A method of treating a disorder modulated by the GPR40 receptor claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .17. A method of treating a disorder claim 1 , wherein said disorder is affected by the agonism of the GPR40 receptor claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .18. The method of wherein said disorder is selected from the group consisting of Type II diabetes mellitus claim 17 , obesity claim 17 , obesity-related disorders claim 17 , impaired glucose tolerance claim 17 , insulin resistance claim 17 , metabolic syndrome claim 17 , other cardiovascular risk factors such as hypertension and cardiovascular risk factors related to unmanaged cholesterol and/or lipid levels claim 17 , osteoporosis claim 17 , inflammation claim 17 , and eczema.19. A ...

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Номер записи: 56
14-01-2016 дата публикации

Locked nucleic acid inhibitor mir-145 and uses thereof

Номер: US20160010091A1
Автор: Anita G. Seto, Christina M. DALBY, Eva Van Rooij, Kathryn H. ROBINSON, Rusty Montgomery, Thomas G. HULLINGER
Принадлежит: Miragen Therapeutics Inc

The present invention provides oligonucleotides with chemical motifs that are miR-145 inhibitors. The oligonucleotides can be used for the treatment and prevention of a condition by inhibiting the expression or activity of miR-145 in cells of a subject in need thereof. Methods provided include treating or preventing pulmonary arterial hypertension, neointima formation, restenosis or hypertension in a subject in need thereof by administering to the subject an inhibitor of miR-145 expression or activity. Pharmaceutical compositions and kits comprising miR-145 inhibitors are also disclosed.

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Номер записи: 57
08-01-2015 дата публикации

HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING THEM, USE AND PROCESSES FOR THE PREPARATION THEREOF

Номер: US20150011535A1
Автор: Heckel Armin, KLEY Joerg
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to compounds of general formula (I) 2. The compound of formula (I) according to claim 1 , wherein{'sub': 2', '2, 'A and A′ are both —CH—CH—;'}{'sup': 1', '2', '3', '4', '5(+)', '(−), 'R is —NRRor —NRRRX;'}X is halogen;{'sup': 1', '2, 'claim-text': [{'sub': 2', '3', '2', '3', '2', '2', '2-4', '3', '2', '1-3', '1-3', '1-4', '1-4', '1-4', '1-3, 'sup': +', '−', '12', '2', '11', '13', '6', '7, 'H, —C(NH)NH, —CN(CH)N(CH)Z, —C-alkyl-N(CH)—C-alkyl-phenyl-R, —C-alkyl-COOH, —C-alkyl-CO—Y—R, —CO-phenyl-CO—O—C—R—CO—C-alkyl, —CO—C-alkyl-NRR,'}, {'sub': 1-3', '3', '3, 'sup': '+', 'CO—C-alkyl-N(CH)'}, {'sub': 3', '1-4', '1-4', '3-7', '1-4', '2', '1-3', '2', '1-3', '2, 'sup': −', '1', '9', '8', '10, 'Z, —CO—C-alkyl-Y—R, —CO—O—C-alkyl-R, —CO—NH—C-cycloalkyl, —CO—NH—C-alkyl, —CH—CO—O—C-alkyl, —CH—CO—O—C-alkyl-phenyl, —SO—R;'}, {'sup': '6', 'sub': 1-3', '1-4', '2', '1-3', '2, 'Ris selected from —C-alkyl, H, —C-alkyl-OH, —CH—CO—O—C-alkyl and —CHCOOH;'}, {'sup': '7', 'sub': 1-3', '1-3', '1-4, 'claim-text': {'sub': 2', '1-3', '2, 'H, —CH—CO—O—C-alkyl and —CHCOOH;'}, 'Ris selected from —C-alkyl, —CO—O—C-alkyl, —C-alkyl-OH,'}, {'sup': '8', 'Ris H or phenyl;'}, {'sup': 9', '6', '7, 'sub': '1-3', 'Ris selected from H, —C-alkyl, —OH, —NRRand ═O;'}, {'sup': '10', 'sub': '1-3', 'Ris C-alkyl or an optionally substituted N-containing nonaromatic heterocycle;'}, {'sup': 11', '+', '−, 'sub': 1-3', '3', '2', '3', '3, 'Ris selected from H, —C-alkyl, ═O, —N(CH)and —N(CH)X;'}, {'sup': '12', 'Ris H or halogen;'}, {'sup': '13', 'sub': '1-4', 'Ris H or —C-alkyl;'}, {'sup': '1', 'Yis an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle,'}, {'sup': '2', 'Yis an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle,'}], 'Rand Rare selected independently from each other from'}{'sup': 1', '2, 'or Rand Rare together with the nitrogen atom they are attached to an optionally substituted 4-7-membered heterocycle containing at least one ...

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Номер записи: 58
08-01-2015 дата публикации

Inhibitors of Protein Kinases

Номер: US20150011576A1
Автор: Allgeier Hans, Augustin Martin, Peraus Gisela, Pleiss Michael A., Schauerte Heike, Stumm Gabriele, Wabnitz Philipp
Принадлежит:

The present invention relates to inhibitors of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to methods of preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases comprising the administration of an effective amount of at least one inhibitor of cyclin-dependent kinases. 2. The method of claim 1 , wherein the pain comprises chronic pain claim 1 , inflammatory pain claim 1 , neuropathic pain claim 1 , or a combination thereof.4. The method of claim 3 , wherein the pain comprises chronic pain claim 3 , inflammatory pain claim 3 , neuropathic pain claim 3 , or a combination thereof.6. The method of claim 5 , wherein the pain comprises chronic pain claim 5 , inflammatory pain claim 5 , neuropathic pain claim 5 , or a combination thereof.7. A method for treatment of a disease selected from the group of pain claim 5 , an inflammatory disorder claim 5 , an immunological disease claim 5 , a proliferative disease claim 5 , an infectious disease claim 5 , a cardiovascular disease and a neurodegenerative disease claim 5 , comprising administering a therapeutically effective amount of at least one compound selected from the group consisting of:{4-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 1);C-{4-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 2); and{4-[4-(2-Methoxy-phenyl)-6-methyl-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 3)to a patient suffering from said disease.8. The method of claim 7 , wherein the pain comprises chronic pain claim 7 , inflammatory pain claim 7 , neuropathic pain claim 7 , or a combination thereof. This application is a division of U.S. patent application Ser. No. 12/451,041, filed on Mar. 3, 2010, which is a U.S. National Stage of PCT/EP2008/054977, filed on Apr. 24, 2008, ...

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Номер записи: 59
10-01-2019 дата публикации

SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS

Номер: US20190010126A1
Автор: COSFORD Nicholas D.P., Dahl Russell, Millan Jose Luis, Pinkerton Anthony B.
Принадлежит:

Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper-mineralization. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. The method of claim 1 , wherein Xis ═C(R)—.9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The method of claim 1 , wherein Ris optionally substituted phenyl or optionally substituted 5- or 6-membered heteroaryl.14. (canceled)15. The method of claim 1 , wherein Rand Rare independently selected from the group consisting of —F claim 1 , —Cl claim 1 , —Br claim 1 , —CN claim 1 , —OMe claim 1 , and —OCF.16. (canceled)17. (canceled)18. (canceled)21. (canceled)22. The method of claim 20 , wherein: A is —C(O)—O—R claim 20 , wherein Ris selected from hydrogen claim 20 , optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , and optionally substituted phenyl.23. (canceled)24. (canceled)25. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rtogether with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino.26. The method of claim 25 , wherein the optionally substituted heterocycloamino is an optionally substituted pyrrolidine claim 25 , an optionally substituted piperidine claim 25 , an optionally substituted morpholine claim 25 , or an optionally substituted piperazine.27. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Ris hydrogen and Ris optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , or optionally substituted phenyl.28. (canceled)29. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rare hydrogen.30. (canceled)31. (canceled)32. (canceled)33. The method of claim 1 , wherein the vascular calcification is an arterial calcification.34. The method of ...

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Номер записи: 60
10-01-2019 дата публикации

PERK INHIBITORS AND USES THEREOF IN TREATING DISEASES ASSOCIATED WITH AGGREGATION-PRONE PROTEINS

Номер: US20190010130A1
Автор: EIGER Hagit, Ganz Javier, LEDERKREMER Gerardo Zelmar, LEITMAN Julia, Offen Daniel, PORTNOY Moshe
Принадлежит: Ramot at Tel-Aviv University Ltd.

Compounds represented by Formula I are disclosed herein, 116-. (canceled)19. The method of claim 18 , wherein Rand Rare each other than bromo.20. The method of claim 18 , wherein when R is OR′ claim 18 , and R′ is methyl claim 18 , Rand Rare each other than bromo.21. The method of claim 18 , wherein Ra is methyl.22. The method of claim 18 , wherein Rand Rare each hydrogen.23. The method of claim 18 , wherein R-Rare each hydrogen.24. The method of claim 18 , wherein R-Rare each hydrogen.25. The method of claim 18 , wherein R is OR′.26. The method of claim 25 , wherein R′ is methyl.28. The method of claim 18 , wherein R is OH.31. The method of claim 30 , wherein Ra is methyl.32. The method of claim 30 , wherein Rand Rare each hydrogen.33. The method of claim 30 , wherein R-Rare each hydrogen.34. The method of claim 30 , wherein R-Rare each hydrogen.35. The method of claim 30 , wherein R is OR′.36. The method of claim 35 , wherein R′ is methyl.38. The method of claim 30 , wherein R is OH. The present invention, in some embodiments thereof, relates to therapy, and more particularly, but not exclusively, to compounds which inhibit pancreatic endoplasmic reticulum kinase (PERK) activity and which are usable in treating diseases associated with aggregation-prone proteins, such as Huntington's disease.Protein aggregation is a biological phenomenon in which misfolded proteins form, either intracellularly or extracellularly, aggregates which are often toxic. Aggregation-prone proteins produce cellular stress, toxicity and death and are the cause of many of the neurodegenerative diseases, including, for example, ALS, Alzheimer's, Parkinson's and prion disease.Proteins fold into their native conformation and undergo a series of post-translational modifications in the endoplasmic reticulum (ER) as part of the normal process of cellular homeostasis. Disruption of cellular protein folding results in ER stress. Cells respond to ER stress by activation of the unfolded protein ...

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Номер записи: 61
09-01-2020 дата публикации

PRECIPITATION METHOD AND SYNTHESIS METHOD OF 2,6-DIAMINO-3,5-DINITROPYRAZINE-1-OXIDE

Номер: US20200010431A1
Автор: Barthet Christelle, Beaucamp Arnaud, Pasquinet Eric, Pin Nicolas, Wuillaume Anne
Принадлежит:

A method for precipitating as particles 2,6-diamino-3,5-dinitropyrazine-1-oxide (or ANPZO) present in an acid medium, which comprises adding the acid medium to an aqueous solution and which is characterized in that the aqueous solution comprises a nitrate salt. Further disclosed is a method for synthesizing ANPZO implementing this precipitation method. The synthesis method comprises converting 2,6-diaminopyrazine-1-oxide (or DAPO) into ANPZO by nitration in an acid medium, and then precipitating as particles the ANPZO by adding the acid medium to an aqueous solution, and is characterized in that the aqueous solution comprises a nitrate salt. 1. A method for precipitating as particles 2 ,6-diamino-3 ,5-dinitropyrazine-1-oxide present in an acid medium , the medium comprising nitric acid or a nitrate salt or a mixture thereof , and at least one strong acid other than nitric acid , the method comprising adding the acid medium to an aqueous solution comprising a nitrate salt.2. A method for synthesizing particles of 2 ,6-diamino-3 ,5-dinitropyrazine-1-oxide , comprising:converting 2,6-diaminopyrazine-1-oxide into 2,6-diamino-3,5-dinitroyrazine-1-oxide by nitrating 2,6-diaminopyrazine-1-oxyde in an acid medium comprising nitric acid or a nitrate salt or a mixture thereof, and at least one strong acid other than nitric acid, and thenprecipitating as particles 2,6-diamino-3,5-dinitropyrazine-1-oxide by adding the acid medium to an aqueous solution comprising a nitrate salt.3. The method of claim 1 , wherein the nitrate salt is sodium nitrate claim 1 , potassium nitrate or ammonium nitrate.4. The method of claim 1 , wherein the aqueous solution comprises between 110 g and 2 claim 1 ,500 g of the nitrate salt for 1 litre of water.5. The method of claim 1 , wherein a ratio of a volume of the aqueous solution to a volume of the acid medium is comprised between 0.5 and 10.6. The method of claim 1 , wherein the acid medium is gradually added to the aqueous solution.7. The method ...

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Номер записи: 62
19-01-2017 дата публикации

DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFONDIIMINE GROUP

Номер: US20170015634A1
Автор: BOHLMANN Rolf, Bömer Ulf, Lienau Philip, Lucking Ulrich, SCHOLZ Arne, Siemeister Gerhard
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The present invention relates to 5-fluoro pyrimidine derivatives containing a sulfondiimine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I). 3. The compound of general formula (I) according to claim 1 , wherein{'sup': 9a', '9b, 'Rand Rrepresent a hydrogen atom,'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.7. The compound of general formula (I) according to claim 1 , wherein{'sup': '6', 'Rrepresents a fluoro atom;'}{'sup': '7', 'Rrepresents a hydrogen atom,'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.8. The compound of general formula (I) according to claim 1 , wherein{'sup': '3', 'sub': '5', 'Rrepresents a group selected from a fluoro atom and —SF;'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.11. The compound according to claim 1 , which is5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-{3-fluoro-5-[(S-methylsulfonodiimidoyl)methyl]phenyl}pyrimidin-2-amine;(rac)-N-{3-[(N,S-Dimethylsulfonodiimidoyl)methyl]-5-fluorophenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine;(rac)-5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-{3-fluoro-5-[(S-methyl-N-phenylsulfonodiimidoyl)methyl]phenyl}pyrimidin-2-amine;(rac)-5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-(3-fluoro-5-{[S-methyl-N-(prop-2-yn-1-yl)sulfonodiimidoyl]methyl}phenyl)pyrimidin-2-amine;{'sup': '6', '(rac)-[(3-Fluoro-5-{[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino}benzyl)(imino)methyl-λ-sulfanylidene]cyanamide;'}{'sup': '6', '(rac)-3-{[(3-Fluoro-5-{[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino}benzyl)(imino)methyl-λ-sulfanylidene]amino}propan-1-ol;'}{'sup': '6', '4 ...

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Номер записи: 63
18-01-2018 дата публикации

IMPROVED PROCESS FOR PREPARING STATIN PRECURSOR

Номер: US20180016241A1
Автор: Bessembinder Karin Henderika Maria, De Lange Ben, Heemskerk Dennis
Принадлежит:

The present invention relates to a process for preparing a statin precursor, which process comprises a first reaction step, wherein a hydroxy-pyrimidine-carbonitrile is reacted with an organic sulfonyl halide to form the sulfonate-pyrimidine-carbonitrile; a second reaction step, wherein the sulfonate-pyrimidine-carbonitrile is reacted with N-methylmethane sulfonamide to form a pyrimidinyl-sulfonamide; and optionally a third reaction step, wherein the pyrimidinyl-sulfonamide is reacted with a reducing agent. All steps are conducted in toluene as the main solvent. 2. The process according to wherein toluene is present in steps (a) claim 1 , (b) and (c).4. The process according to claim 1 , wherein the first and second temperature are independently chosen to lie in the range of 50 to 110° C.5. The process according to claim 1 , wherein the intermediate mixture is contacted with N-methylmethane sulfonamide by adding the intermediate mixture to a sulfonamide mixture comprising N-methylmethane sulfonamide in toluene.6. The process according to claim 5 , wherein the intermediate mixture is added to the mixture comprising N-methylmethane sulfonamide over a period of at least 1 hour.7. The process according to claim 5 , wherein the mixture comprising N-methylmethane sulfonamide further comprises a base.8. The process according to claim 5 , wherein the sulfonamide mixture comprises 1-60 wt. % N-methylmethane sulfonamide claim 5 , relative to the total weight of toluene in the sulfonamide mixture.9. The process according to claim 1 , wherein the organic sulfonyl halide is selected from the group consisting of methanesulfonyl chloride claim 1 , ethanesulfonyl chloride claim 1 , trifluoromethanesulfonyl chloride claim 1 , methanesulfonyl bromide claim 1 , benzenesulfonyl chloride claim 1 , benzenesulfonyl bromide claim 1 , p-toluenesulfonyl chloride claim 1 , p-toluenesulfonyl bromide claim 1 , p-toluenesulfonyl fluoride claim 1 , 4-chlorobenzenesulfonyl chloride claim 1 , 2- ...

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Номер записи: 64
16-01-2020 дата публикации

Therapeutic Agents

Номер: US20200017860A1
Автор: Aitman Tim, Oliver-Perez Eduardo, Wilkins Martin, Zhao Lan
Принадлежит: IMPERIAL INNOVATIONS LIMITED

The present invention related to identification of therapeutic agents of the treatment, diagnosis, and prevention of pulmonary hypertension. 126- (canceled)27. A method of treating or preventing pulmonary hypertension in a subject , the method comprising: (i) modulating ZIP12 protein levels , (ii) genetic disruption of the Slc39a12 gene , or (iii) inhibiting Slc39a12 gene expression , in a subject in need of such treatment.28. A method according to claim 27 , wherein ZIP12 is modulated by altering the expression of gene Slc39a12.29. A method according to claim 27 , wherein an inhibitor of ZIP12 expression is administered to the subject.30. A method according to claim 29 , wherein said inhibitor is a nucleic acid claim 29 , an antisense oligonucleotide claim 29 , siRNA claim 29 , or a dsRNA.31. A method according to claim 29 , wherein the inhibitor is an antisense oligonucleotide claim 29 , siRNA claim 29 , or dsRNA which specifically binds to a portion of an mRNA encoding ZIP12.32. A method according to claim 29 , wherein the inhibitor is an antisense oligonucleotide claim 29 , siRNA claim 29 , or dsRNA which specifically binds to a portion of the mRNA product of Slc39a12.33. A method according to claim 27 , wherein the Slc39a12 gene is disrupted by a Zinc finger nuclease.34. A method according to claim 27 , wherein ZIP12 is modulated claim 27 , the Slc39a12 gene is disrupted or the Slc39a12 gene expression is inhibited claim 27 , by targeting exon 8 of the Slc39a12 gene.35. A method according to claim 27 , wherein the pulmonary hypertension to be prevented or treated is caused by hypoxic stress. This application is a divisional of U.S. patent application Ser. No. 15/747,292 filed Jan. 24, 2018, now abandoned, which is a National Phase of International Application No. PCT/GB2016/052297 filed Jul. 27, 2016, currently pending, which designated the U.S. and that International Application was published under PCT Article 21(2) in English, which also includes a claim of ...

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Номер записи: 65
10-02-2022 дата публикации

Inhibitors of glucose-6-phosphate dehydrogenase for treating cardiovascular and pulmonary conditions

Номер: US20220040202A1
Автор: Sachin A. GUPTE
Принадлежит: Ichor LLC

The present disclosure provides for methods of treating or preventing a cardiovascular disorder and/or a related pulmonary disorder in a subject. In certain embodiments, the method comprises administering a therapeutically effective amount of an inhibitor of Glucose-6-phosphate dehydrogenase (G6PD), or a pharmaceutically acceptable salt, non-salt amorphous form, solvate, poly-morph, tautomer or prodrug thereof.

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Номер записи: 66
26-01-2017 дата публикации

INTERMEDIATE COMPOUND FOR PREPARING ROSUVASTATIN CALCIUM AND METHOD FOR PREPARING ROSUVASTATIN CALCIUM THEREFROM

Номер: US20170022169A1
Автор: DONG Changming, GAGE James, HONG Hao, LI Jiuyuan, SHEN Litao, ZHANG LEI
Принадлежит:

Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost. 3. The method according to claim 2 , wherein Ris tert-butyl claim 2 , tert-pentyl claim 2 , cyclopentyl or cyclohexyl.4. The method according to claim 2 , wherein the step of combining formula (I) with formula (II) comprises: adding the intermediate compound formula (I) into an organic solvent claim 2 , cooling down to −80 to −20° C. claim 2 , then adding an alkali claim 2 , adding dropwise a solution of formula (II) at −80 to −20° C. claim 2 , reacting at −80 to −20° C. for 1 to 3 hours after the addition is completed claim 2 , warming up to −45 to 25° C. and reacting until the reaction is completed claim 2 , quenching the reaction claim 2 , extracting claim 2 , concentrating the extraction solution claim 2 , and adding a solvent to the crude product obtained by concentrating claim 2 , and crystallizing formula (III).5. The method according to claim 2 , wherein the alkali is selected from the group consisting of sodium hydride claim 2 , butyllithium claim 2 , lithium diisopropylamide claim 2 , lithium hexamethyldisilazide claim 2 , sodium hexamethyldisilazide claim 2 , 2 claim 2 ,2 claim 2 ,6 claim 2 ,6-tetramethylpiperidinylmagnesium chloride claim 2 , 2 claim 2 ,2 claim 2 ,6 claim 2 ,6-tetramethylpiperidine lithium claim 2 , potassium hexamethyldisilazide claim 2 , lithium ...

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Номер записи: 67
17-04-2014 дата публикации

SUBSTITUTED PYRIDYL AMIDE COMPOUNDS AS MODULATORS OF THE HISTAMINE H3 RECEPTOR

Номер: US20140107105A1
Автор: Keith John M., Letavic Michael A., Ly Kiev S., Mani Neelakandha S., Mills John E., Pandit Chennagiri R., Villani Frank J., Zhong Hua
Принадлежит: Janssen Pharmaceutica NV

Certain substituted pyridyl amide compounds are histamine Hreceptor modulators useful in the treatment of histamine Hreceptor-mediated diseases. 2. A compound as defined in claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , sec-butyl claim 1 , or tert-butyl.3. A compound as defined in claim 1 , wherein Ris methyl or isopropyl.4. A compound as defined in claim 1 , wherein Ris cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl.5. A compound as defined in claim 1 , wherein m is 1.6. A compound as defined in claim 1 , wherein m is 2.7. A compound as defined in claim 1 , wherein X is N claim 1 , Y is CR claim 1 , and Ris —Z—Ar.8. A compound as defined in claim 1 , wherein X is CH claim 1 , Y is N claim 1 , and Ris —Z—Ar.9. A compound as defined in claim 1 , wherein X is N claim 1 , Y is CR claim 1 , and Ris —H claim 1 , where Ris —Z—Ar.10. A compound as defined in claim 1 , wherein Ris —CN claim 1 , —CONH claim 1 , or —CHNH.11. A compound as defined in claim 1 , wherein Ris —H.12. A compound as defined in claim 1 , wherein Z is O.13. A compound as defined in claim 1 , wherein Z is S.14. A compound as defined in claim 1 , wherein Ar is a phenyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , or pyrazinyl group claim 1 , each unsubstituted or substituted with one claim 1 , two claim 1 , or three Rsubstituents.15. A compound as defined in claim 1 , wherein Ar is a phenyl group unsubstituted or substituted with one claim 1 , two claim 1 , or three Rsubstituents.16. A compound as defined in claim 1 , wherein Ar is a 4-halophenyl group.17. A compound as defined in claim 1 , wherein Ar is phenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 4-methylsulfanylphenyl claim 1 , 3-chlorophenyl claim 1 , 3-fluorophenyl claim 1 , 4-chloro-3- ...

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Номер записи: 68
17-04-2014 дата публикации

3,5-DIAMINO-6-CHLORO-N-(N-(4-(4-(2-(HEXYL(2,3,4,5,6-PENTAHYDROXYHEXYL)AMINO)ETHOXY)PHENYL)BUTYL)CARBAMIMIDOYL)PYRAZINE-2-CARBOXAMIDE

Номер: US20140107133A1
Автор: JOHNSON Michael R.
Принадлежит: PARION SCIENCES, INC.

The present invention relates to the compound of the formula: 127-. (canceled)29. The method of wherein the effective amount of a compound of formula (Ia) claim 28 , or a pharmaceutically acceptable salt thereof claim 28 , is delivered by inhalation.30. The method of wherein the effective amount of a compound of formula (Ia) claim 29 , or a pharmaceutically acceptable salt thereof claim 29 , is delivered by inhalation using a nebulizer claim 29 , a metered dose inhaler claim 29 , or a dry powder inhaler.31. The method of wherein the compound of formula (Ia) claim 28 , or a pharmaceutically acceptable salt thereof claim 28 , is delivered at a dose of from about 0.1 μg to about 1 claim 28 ,000 μg.32. The method of wherein the compound of formula (Ia) claim 28 , or a pharmaceutically acceptable salt thereof claim 28 , is delivered at a dose of from about 0.5 μg to about 0.5 mg.34. The method of wherein the effective amount of a compound of formula (Ia) claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , is delivered by inhalation.35. The method of wherein the effective amount of a compound of formula (Ia) claim 34 , or a pharmaceutically acceptable salt thereof claim 34 , is delivered by inhalation using a nebulizer claim 34 , a metered dose inhaler claim 34 , or a dry powder inhaler.36. The method of wherein the compound of formula (Ia) claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , is delivered at a dose of from about 0.1 μg to about 1 claim 33 ,000 μg.37. The method of wherein the compound of formula (Ia) claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , is delivered at a dose of from about 0.5 μg to about 0.5 mg.39. The method of wherein the effective amount of a compound of formula (Ia) claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , is delivered by inhalation.40. The method of wherein the effective amount of a compound of formula (Ia) claim 39 , or a pharmaceutically acceptable salt ...

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Номер записи: 69
22-01-2015 дата публикации

ARYLALKYL ESTERS OF 4-AMINO-6-(SUBSTITUTED PHENYL)-PICOLINATES AND 6-AMINO-2-(SUBSTITUTED PHENYL)-PYRIMIDINECARBOXYLATES AND THEIR USE AS SELECTIVE HERBICIDES FOR CROPS

Номер: US20150025238A1
Автор: Eckelbarger Joseph D., Epp Jeffrey B., Guenthenspberger Katherine A., Lowe Christian T., Schmitzer Paul R., Siddall Thomas L., Yerkes Carla N.
Принадлежит: DOW AGROSCIENCES LLC

Arylalkyl esters of 4-aminopicolinic acids and 6-amino-4-pyrimidinecarboxylates are herbicides for control of weeds especially those species common to rice and wheat cropping systems and in pasture management programs. 2. The compound of in which Y represents substituted phenyl.3. The compound of in which Z represents Cl claim 1 , —CH═CHor OCH.4. The compound of in which Rand Rrepresent H.5. The compound of in which Rrepresents a benzyl.6. The compound of in which Rrepresents an unsubstituted or ortho- claim 1 , meta- or para-monosubstituted benzyl. This application is a divisional of U.S. Non-Provisional application Ser. No. 13/356,668 filed Jan. 24, 2012 which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/435,925 filed Jan. 25, 2011.This invention relates to certain novel esters of 4-amino-6-(substituted phenyl)-picolinic acids and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylic acids and to the use of these compounds as herbicides for control of weeds especially those species common to rice and wheat cropping systems and in pasture management programs.A number of picolinic acids and their pesticidal properties have been described in the art. U.S. Pat. No. 6,784,137 B2 and U.S. Pat. No. 7,314,849 B2 disclose a genus of 4-amino-6-arylpicolinic acids and their derivatives and their use as selective herbicides, particularly for rice and cereals such as wheat and barley. WO 2005/063721 A1, WO 2007/082076 A1, U.S. Pat. No. 7,863,220 B2, U.S. Pat. No. 7,300,907 B2, U.S. Pat. No. 7,642,220 B2, and U.S. Pat. No. 7,786,044 B2 disclose certain 6-amino-2-substituted-4-pyrimidinecarboxylic acids and their derivatives and their use as herbicides. It has now been discovered that certain esters of 4-amino-6-(substituted phenyl)picolinic acids and of 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylic acids can provide superior weed control especially in rice and wheat cropping systems and in pasture management programs.Certain arylalkyl esters of ...

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Номер записи: 70
28-01-2021 дата публикации

3,5-DIAMINO-6-CHLORO-N-(N-(4-(4-(2-(HEXYL(2,3,4,5,6-PENTAHYDROXYHEXYL)AMINO)ETHOXY)PHENYL)BUTYL)CARBAMIMIDOYL)PYRAZINE-2-CARBOXAMIDE

Номер: US20210024471A1
Автор: JOHNSON Michael R.
Принадлежит: PARION SCIENCES, INC.

The present invention relates to the compound of the formula: 127-. (canceled)29. The method of claim 28 , wherein the reaction is carried out in the presence of a base.30. The method of further comprising a step of purification claim 28 , resolution of stereoisomers claim 28 , crystallization claim 28 , and/or preparation of a salt form.32. The method of claim 31 , wherein the reaction is carried out in the presence of a base.33. The method of further comprising a step of hydrolyzing compound (19) claim 31 , or a salt thereof claim 31 , in the presence of an acid claim 31 , to form compound (Ia) claim 31 , or a salt thereof.35. The method of claim 34 , wherein the reducing agent in step (i) is NaCNBH.36. The method of claim 34 , wherein step (ii) is carried out in the presence of Hand Pd/C.38. The method of claim 37 , wherein step (ii) is carried out in the presence of HCl.39. The method of further comprising a step of purification claim 31 , resolution of stereoisomers claim 31 , crystallization claim 31 , and/or preparation of a salt form.41. The method of claim 40 , wherein the reaction is carried out in the presence of a base.42. The method of further comprising a step of hydrolyzing compound (20) claim 40 , or a salt thereof claim 40 , in the presence of an acid claim 40 , to form compound (Ia) claim 40 , or a salt thereof.44. The method of claim 43 , wherein the reducing agent in step (i) is NaCNBH.45. The method of claim 43 , wherein step (ii) is carried out in the presence of Hand Pd/C. This application is a continuation of and claims priority under 35 U.S.C. § 120 to U.S. patent application U.S. Ser. No. 15/446,877, filed on Mar. 1, 2017, which is a continuation of and claims priority under 35 U.S.C. § 120 to U.S. patent application U.S. Ser. No. 14/132,194, filed on Dec. 18, 2013, now issued U.S. Pat. No. 9,586,910, which is a divisional of and claims priority under 35 U.S.C. § 120 to U.S. patent application U.S. Ser. No. 13/533,911, filed on Jun. 26, ...

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Номер записи: 71
24-04-2014 дата публикации

NOVEL ANTIVIRAL THERAPIES

Номер: US20140113923A1
Автор: Balzarini Jan, Mazik Monika
Принадлежит:

The field of the invention relates to the use of carbohydrate binding compounds as a medicine, their use to treat or prevent viral infections, their use to manufacture a medicine to treat or prevent viral infections and their use in a vaccination strategy. The present invention relates to the use of said compounds to manufacture a medicine to treat or prevent viral infections of subject, more in particular infections with viruses having glycosilated envelope proteins such as Retroviridae (i.e., Lentivirinae), like HIV (human immunodeficiency virus), Flaviviridae, like HCV (hepatitis C virus), Hepadnaviridae, like HBV (hepatitis B virus), Coronaviridae, like SARS corona virus, and Orthomyxoviridae, like influenza A, B, or C. 15-. (canceled)17. The method of claim 16 , wherein said viral infection is an infection with a virus having a glycosilated envelope protein. The field of the invention relates to the use of carbohydrate binding compounds as a medicine, their use to treat or prevent viral infections, their use to manufacture a medicament to treat or prevent viral infections and their use in a vaccination strategy. The present invention relates to the use of said compounds to manufacture a medicine to treat or prevent viral infections of subjects, more in particular infections with viruses having glycosilated envelop proteins such as Retroviridae (i.e. Lentivirinae), like HIV (human immunodeficiency virus), Flaviviridae like, HCV (hepatitis C virus), Hepadnaviridae, like HBV (hepatitis B virus), Coronaviridae, like SARS-CoV, and Orthomyxoviridae, like influenza virus A, B and C.Viral infections remain a major medical problem worldwide because of a lack of efficient therapy, prevention or vaccination strategy and because of the rapid development of resistance. Many virusses and virus families causing problematic disorders can be identified. The family of the Flaviviridae (I.e. Dengue virus, HCV, Yellow Fever virus, West Nile virus) can cause major health problems ...

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Номер записи: 72
29-01-2015 дата публикации

ANTI-MALARIAL AGENTS

Номер: US20150031682A1
Автор: Chibale Kelly, Waterson David, Witty Michael John, Younis Yassir
Принадлежит:

The present invention is related to a use of aminopyrazine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to aminopyrazine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation. 127-. (canceled)29. The aminopyrazine according to claim 28 , wherein X is N.30. The aminopyrazine according to claim 28 , wherein X is CR.31. The aminopyrazine according to claim 28 , wherein Y is CF.32. The aminopyrazine according to claim 28 , wherein Y is —C(O)—NHR.33. The aminopyrazine according to claim 28 , wherein Y is SO—R.34. The aminopyrazine according to claim 28 , wherein Ris SO—R.35. The aminopyrazine according to claim 28 , wherein Ris SO—R.36. The aminopyrazine according to claim 28 , wherein Ris SO—Rand Ris optionally substituted C-Calkyl.37. The aminopyrazine according to claim 28 , wherein Ris —C(O)—R.38. The aminopyrazine according to claim 37 , wherein NRRform together an optionally substituted heterocycloalkyl.39. The aminopyrazine according to claim 37 , wherein Rand Rare independently selected from H and optionally substituted C-Calkyl.40. The aminopyrazine according to claim 28 , wherein the aminopyrazine is selected from the following group:3-(6-methoxypyridin-3-yl)-5-(4-(methylsulfonyl)phenyl)pyrazin-2-amine;5-(4-(methylsulfonyl)phenyl)-3-(4-(trifluoromethyl)phenyl)pyrazin-2-amine;5-(4-(methylsulfonyl)phenyl)-3-(6-(trifluoromethyl)pyridin-3-yl)pyrazin-2-amine;4-(5-amino-6-(4-(trifluoromethyl)phenyl)pyrazin-2-yl)benzamide;4-(5-amino-6-(6-(trifluoromethyl)pyridin-3-yl)pyrazin-2-yl)benzamide;(4-(5-amino-6-(4-(trifluoromethyl)phenyl)pyrazin-2-yl)phenyl)(4-methylpiperazin-1-yl)methanone;(4-(5-amino-6-(6-(trifluoromethyl)pyridin-3-yl)pyrazin-2-yl)phenyl)(4-methyl piperazin-1-yl)methanone;(4-(5-amino-6-(4-(trifluoromethyl)phenyl)pyrazin-2-yl)phenyl)(piperazin-1-yl) methanone;(4-(5-amino-6-(6-(trifluoromethyl)pyridin-3-yl) ...

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Номер записи: 73
29-01-2015 дата публикации

MEGLUMINE SALT OF 6-FLUORO-3-HYDROXY-2-PYRAZINE CARBOXAMIDE

Номер: US20150031885A1
Автор: Nakamatsu Namika, Nakashima Takayoshi, Takakura Keiko, Takeshima Sakiko
Принадлежит: Toyama Chemical Co., Ltd.

A preparation replete with a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazine carboxamide has superior solubility, and is useful as a preparation for injection. 111-. (canceled)12. A process for producing a lyophilized preparation comprising a crystal of a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide , the process comprising:(1) cooling an aqueous solution comprising 6-fluoro-3-hydroxy-2-pyrazinecarboxamide and meglumine to produce a frozen product;(2) increasing the temperature of the frozen product;(3) cooling the frozen product again; and(4) carrying out lyophilization.13. The process according to claim 12 , wherein in (2) the temperature of the frozen product is increased to a temperature within the range of −20 to −5° C. The present invention relates to a meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide (hereinafter referred to as “Compound A”), an injectable preparation containing the same and a process thereof.These days, worldwide pandemic has been caused by H1N1 influenza virus and occurrence of pandemic by a further virulent virus in the future is a concern.At present, as therapeutic agents for influenza, e.g., Oseltamivir, Zanamivir, Peramivir, Laninamivir and Amantadine are used. However, these therapeutic agents have, for example, the following drawbacks. Oseltamivir cannot be administered to patients having difficulty in oral administration. It is difficult to administer Zanamivir to children and aged persons. It takes a long time to administer Peramivir. Amantadine is ineffective against Type B influenza virus and resistant viruses have emerged. Laninamivir is an inhalation drug, which is not suitable to patients with dementia and a severe disease and it is difficult to administer it to children.A further superior therapeutic agent for influenza has been desired. Particularly, an injection that can be administered to patients having difficulty in oral administration, children and aged persons has been desired.Meanwhile, many ...

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Номер записи: 74
01-02-2018 дата публикации

Method for preparing prostacyclin receptor agonist

Номер: US20180029998A1
Автор: Chi Ma, Fanghui TANG, Qiang JIA
Принадлежит: Seasons Biotechnology (taizhou) Co Ltd

The present invention relates to preparation methods of a prostacyclin receptor agonist of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and its intermediates. These methods are simple and convenient to operate, environment-friendly and suitable for industrial production to obtain the product with good yield and high purity.

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Номер записи: 75
17-02-2022 дата публикации

LUMINOGENS FOR BIOLOGICAL APPLICATIONS

Номер: US20220048923A1
Автор: Chen Ming, Qi Ji, QIN Wei, TANG Benzhong, Zhang Pengfei
Принадлежит:

A compound comprises a donor and an acceptor, wherein at least one donor (“D”) and at least one acceptor (“A”) may be arranged in an order of D-A; D-A-D; A-D-A; D-D-A-D-D; A-A-D-A-A; D-A-D-A-D; and A-D-A-D-A. The compound may be selected from the group consisting of: MTPE-TP, MTPE-TT, TPE-TP A-TT, PTZ-BT-TP A, NPB-TQ, TPE-TQ-A, MTPE-BTSe, DCDPP-2TP A, DCDPP-2TPA4M, DCDP-2TPA, DCDP-2TPA4M, TTS, ROpen-DTE-TPECM, and RClosed-DTE-TPECM. The compound may be used as a probe and may be functionalized with special targeted groups to image biological species. As non-limiting examples, the compound may be used in cellular cytoplasms or tissue imaging, blood vessel imaging, in vivo fluorescence imaging, brain vascular imaging, sentinel lymph node mapping, and tumor imaging, and the compound may be used as a photoacoustic agent. 2. The compound of claim 1 , wherein at least one donor and at least one acceptor are arranged in an order selected from the group consisting of:Donor-Acceptor,Donor-Acceptor-Donor,Acceptor-Donor-Acceptor,Donor-Donor-Acceptor-Donor-Donor,Acceptor-Acceptor-Donor-Acceptor-Acceptor,Donor-Acceptor-Donor-Acceptor-Donor, andAcceptor-Donor-Acceptor-Donor-Acceptor.6. The compound of claim 1 , wherein the compound exhibits aggregation-induced emission (AIE).7. A probe comprising the compound of claim 1 , wherein the probe is a far red/near-infrared (FR/NIR) fluorescent probe.8. The probe of claim 7 , wherein the compound is functionalized with special targeted groups to image biological species.9. The probe of claim 7 , wherein the compound is in a PEG matrix is in a form of nanoparticles.10. The probe of claim 9 , wherein the nanoparticles can be incubated with cells and used to image cellular cytoplasms.15. The compound of claim 11 , wherein the compound exhibits aggregation-induced emission (AIE).16. A probe comprising the compound of claim 11 , wherein the probe is a red/near-infrared fluorescent probe.17. The probe of claim 16 , wherein the compound is ...

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Номер записи: 76
04-02-2021 дата публикации

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS

Номер: US20210032213A1
Автор: Boehm Marcus, Huang Liming, Martinborough Esther, Sainz Marcos, Selfridge Brandon, Yeager Adam
Принадлежит:

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I). 3. The method of claim 2 , wherein the MRGPR X4 dependent condition is a condition that is caused by the activation of MRGPR X4 by a bile acid or analog thereof.4. The method of wherein the MRGPR X4 dependent condition is an itch associated condition claim 2 , a pain associated condition claim 2 , or an autoimmune disorder.5rubra. The method of wherein the itch associated condition is chronic itch claim 4 , cholestatic pruritus claim 4 , contact dermatitis claim 4 , allergic blepharitis claim 4 , anemia claim 4 , atopic dermatitis claim 4 , bullous pemphigoid claim 4 , candidiasis claim 4 , chicken pox claim 4 , cholestasis claim 4 , end-stage renal failure claim 4 , hemodialysis claim 4 , contact dermatitis claim 4 , dermatitis herpetiformis claim 4 , diabetes claim 4 , drug allergy claim 4 , dry skin claim 4 , dyshidrotic dermatitis claim 4 , ectopic eczema claim 4 , eczema claim 4 , erythrasma claim 4 , folliculitis claim 4 , fungal skin infection claim 4 , hemorrhoids claim 4 , herpes claim 4 , HIV infection claim 4 , Hodgkin's disease claim 4 , hyperthyroidism claim 4 , iron deficiency anemia claim 4 , kidney disease claim 4 , leukemia claim 4 , liver disease claim 4 , lymphoma claim 4 , malignancy claim 4 , multiple myeloma claim 4 , neurodermatitis claim 4 , onchocerciasis claim 4 , Paget's disease claim 4 , pediculosis claim 4 , polycythemia vera claim 4 , pruritus ani claim 4 , pseudorabies claim 4 , psoriasis claim 4 , rectal prolapse claim 4 , scabies claim 4 , schistosomiasis claim 4 , scleroderma claim 4 , severe stress claim 4 , stasia dermatitis claim 4 , swimmer's itch claim 4 , thyroid disease claim 4 , tinea cruris claim 4 , uremic pruritus claim 4 , or urticaria.6. The ...

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Номер записи: 77
04-02-2021 дата публикации

NOVEL GLUTAMINASE INHIBITORS

Номер: US20210032236A1
Автор: Babu Govindarajulu, Bhavar Prashant K, Merikapudi Gayatri Swaroop, Vakkalanka Swaroop K., Viswanadha Srikant
Принадлежит:

The present disclosure provides compounds of formula (I) to (III) as glutaminase inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of diseases or disorders involving glutamine. 9. A compound of claim 1 , wherein P and Q are each independently selected from —NRC(═O)—(CRR)— claim 1 , —(CRR)—C(═O)—NR— claim 1 , —C(═O)NR—(CRR)— claim 1 , —(CRR)—NR—C(═O)— claim 1 , —NH—C(═O)—C(RR)— claim 1 , —(CRR)—C(═O)—NH— claim 1 , —NRC(═O)— claim 1 , —NRC(═S)— claim 1 , —NRS(═O)— claim 1 , —C(═O)NR— claim 1 , —C(═S)NR— claim 1 , or —NR—.10. A compound of claim 1 , wherein P and Q are each independently selected from —NRC(═O)—(CRR)— claim 1 , —(CRR)—C(═O)—NRC(═O)— or —NR— claim 1 , wherein Rand R are independently selected from hydrogen claim 1 , substituted or unsubstituted Calkyl claim 1 , halogen claim 1 , hydroxy and substituted or unsubstituted Calkoxy.11. A compound of claim 1 , wherein P and Q are each independently selected from —NH—C(═O)—(CRR)— claim 1 , —(CRR)—C(═O)—NH— claim 1 , —NH—C(═O)— or —NH— claim 1 , wherein Rand Rare hydrogen.12. A compound of claim 1 , wherein{'sub': 2', '2, '(i) each of P and Q are independently —NH—C(═O)—(CH)—, —(CH)—C(═O)—NH—, —NH—C(═O)— or —NH—;'}{'sub': 2', '2, '(ii) P is —(CH)—C(═O)—NH— and Q is —NH—C(═O)—CH—, —NH—C(═O)— or —NH—;'}{'sub': 2', '2, '(iii) P is —(CH)—C(═O)—NH—, —NH—C(═O)— or —NH— and Q is —NH—C(═O)—CH—; or'}{'sub': 2', '2, '(iv) P is —(CH)—C(═O)—NH— and Q is —NH—C(═O)—CH—.'}13. A compound of claim 1 , wherein both P and Q are independently selected from —NH—C(═O)—CH— or —CH—C(═O)—NH—.15. A compound of claim 1 , wherein{'sub': 1', '1-6', '1-3, 'sup': x', 'x, 'Lis absent, substituted or unsubstituted Calkyl or NR, wherein Ris hydrogen or Calkyl;'}{'sub': '2', 'Lis substituted or unsubstituted 3 to 10 membered heterocyclyl; and'}{'sub': 3', '1-6', '1-3, 'sup': x', 'x, 'Lis absent, substituted or unsubstituted Calkyl or NR, wherein Ris hydrogen ...

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Номер записи: 78
04-02-2021 дата публикации

COMPOSITIONS AND METHODS OF MODULATING 15-PGDH ACTIVITY

Номер: US20210032265A1
Автор: Antczak Monika, Bae KiBeom, Desai Amar, Gerson Stanton, Markowitz Sanford, Posner Bruce, Ready Joseph, Tai Hsin-Hsiung, Willson James K.V., Yang Sung Yeun, Zhang Yongyou
Принадлежит:

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors and 15-PGDH activators described herein. 181-. (canceled)82: A method of treating oral and/or gastrointestinal diseases associated with inflammation and/or ulcers in a subject in need thereof , the method comprising:administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.83: The method of claim 82 , wherein the ulcer comprises at least one of a mucosal or submucosal ulcer.84: The method of claim 82 , wherein the gastrointestinal disease comprises at least one of oral ulcers or gastrointestinal ulcers.85: The method of claim 82 , wherein the gastrointestinal disease comprises at least one of colitis claim 82 , gastritis claim 82 , or cryptitis.86: The method of claim 82 , wherein the gastrointestinal disease comprises ulcerative colitis.87: The method of claim 82 , wherein the gastrointestinal disease comprises inflammatory bowel disease.88: The method of wherein the 15-PGDH inhibitor is administered at an amount effective to increase prostaglandin levels in blood or tissue of the subject89: The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal ulcer formation.90: The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal inflammation.92: A method of treating oral and/or gastrointestinal inflammation and/or ulcers in a subject in need thereof claim 82 , the method comprising:administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.93: The method of claim 92 , wherein the subject has at least one of oral ulcers or gastrointestinal ulcers ...

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Номер записи: 79
11-02-2016 дата публикации

Bioavailable Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

Номер: US20160039750A1
Автор: Carlson Glenn Richard, Chortyk Orestes, HORMANN Robert Eugene, Meyer Andrew, Opie Thomas R., Potter David W., Tice Colin M.
Принадлежит: Intrexon Corporation

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene. 16-. (canceled)9. The method of claim 8 , wherein the ecdysone receptor complex is a chimeric ecdysone receptor complex and the DNA construct further comprises a promoter.10. The method of claim 8 , wherein the subject is a plant.11. The method of claim 8 , wherein the subject is a mammal. This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to non-steroidal ligands for natural and mutated nuclear receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene within a host cell using these ligands and inducible gene expression system.Various publications are cited herein, the disclosures of which are incorporated by reference in their entireties. However, the citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.In the field of genetic engineering, precise control of gene expression is a valuable tool for studying, manipulating, and controlling development and other physiological processes. Gene expression is a complex biological process involving a number of specific protein-protein interactions. In order for gene expression to be triggered, such that it produces the ...

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Номер записи: 80
09-02-2017 дата публикации

ENDOPARASITE CONTROL AGENT

Номер: US20170037029A1
Автор: Kita Kiyoshi, Oda Masatsugu, Suwa Akiyuki, Tanaka Koji
Принадлежит:

An object of the present invention is to provide a novel endoparasite control agent as a parasiticide, an antiprotozoal or the like. Provided is an endoparasite control agent comprising a carboxamide derivative represented by the general formula (I): 110-. (canceled)12. The method according to claim 11 , wherein the effective amount of the endoparasite control agent is orally or parenterally administered to a non-human mammal.13. The method according to claim 12 , wherein the non-human mammal is a domestic animal.15. The method according to claim 11 , wherein A is a (C-C) alkylene group; or a substituted (C-C) alkylene group having one or more substituents selected from a halogen atom claim 11 , a (C-C) alkyl group and a (C-C) cycloalkyl group.16. The endoparasite control agent method according to claim 11 , wherein B is selected from the group consisting of B5 to B8. The present invention relates an endoparasite control agent comprising a carboxamide derivative or a salt thereof as an active ingredient, and a method for controlling endoparasites, comprising orally or parenterally administering the endoparasite control agent.Generally, parasitosis is caused by infestation of host animals with parasites such as unicellular protists (protozoa), multicellular helminths and arthropods. It is reported that the incidence of parasitosis in advanced countries has been remarkably decreased by improvement of environmental hygiene, but on a global scale, particularly in developing countries, parasitosis still widely prevails and causes tremendous damage.In recent years, even in advanced countries, there has been an increasing trend in the incidence of parasitosis. This is partly because of introduction of infection sources via long- or short-term overseas travelers, and partly because of parasitic infection due to ingestion of food imports, frozen foods, raw meat, fish meat, etc. or via domestic animals and pets. Another problem is that immunodeficiency caused by mass ...

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Номер записи: 81
07-02-2019 дата публикации

Modulators of indoleamine 2,3-dioxygenase

Номер: US20190040023A1
Автор: Hamilton D Dickson, Martha Alicia De La Rosa, Pek Yoke Chong, Vicente Samano, Vincent Wing-Fai TAI, Wieslaw Mieczyslaw Kazmierski
Принадлежит: GlaxoSmithKline Intellectual Property Development Ltd

Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.

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Номер записи: 82
16-02-2017 дата публикации

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Номер: US20170042897A1
Автор: Chen Ning, Chen Xiaoqi, CHEN Yinhong, Cheng Alan C., Connors Richard V., DeBenedetto Mikkel V., Deignan Jeffrey, Dransfield Paul John, Du Xiaohui, Farrell Robert P., FU Zice, HEATH Julie Anne, Hedley Simon J., Horne Daniel B., HOUZE Jonathan, Judd Ted C., Kaller Matthew R., KAYSER Frank, KHAKOO Aarif Yusuf, Kopecky David John, LAI Su-Jen, Ma Zhihua, McGee Lawrence R., MEDINA Julio C., MIHALIC Jeffrey T., Nishimura Nobuko, OLSON Steven H., Pattaropong Vatee, SWAMINATH Gayathri, Wang Xiaodong, Yang Kevin, YEH Wen-Chen
Принадлежит:

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.7. The compound of or the salt thereof claim 6 , the tautomer thereof claim 6 , or the salt of the tautomer claim 6 , wherein Ris in each instance independently selected from CH claim 6 , —F claim 6 , —Cl claim 6 , —Br claim 6 , —CN claim 6 , —CF claim 6 , —OCH claim 6 , —OCHF claim 6 , —OCHCH claim 6 , —C(═O)OCH claim 6 , —C(═O)CH claim 6 , or N(CH).9. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.10. The compound of or the salt thereof claim 9 , the tautomer thereof claim 9 , or the salt of the tautomer claim 9 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.11. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Q is selected from pyrimidinyl claim 1 , pyridyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , imidazolyl claim 1 , phenyl claim 1 , tetrahydropyrimidinonyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclohexyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , pyrazinyl claim ...

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Номер записи: 83
01-05-2014 дата публикации

SELECTIVE PDE4 B INHIBITION AND IMPROVEMENT IN COGNITION IN SUBJECTS WITH BRAIN INJURY

Номер: US20140121221A1
Автор: Adaikkalasamy David J., Atkins Collen M., Dietrich W. Dalton, GURNEY Mark E.
Принадлежит:

Provided herein are methods of improving cognitive ability or memory in a subject that has suffered a brain injury or spinal cord injury by administering a selective PDE4 B inhibitor. 2. (canceled)3. The method of claim 1 , wherein the traumatic brain injury results from one or more concussion events claim 1 , or chronic traumatic encephalopathy (CTE).4. (canceled)5. The method of claim 1 , wherein the improvement to cognitive function comprises improved short term memory claim 1 , improved long term memory claim 1 , improved attention span claim 1 , or improved working memory.6. The method of claim 1 , wherein the cognitive impairment is measurable or has persisted past the acute stage of brain injury claim 1 , or wherein the administration of the selective PDE4 B inhibitor is initiated during a subsequent chronic stage following the brain injury.7. The method of claim 1 , wherein the cognitive impairment is measurable or has persisted for at least six weeks following a brain injury.8. The method of claim 1 , wherein administration of the selective PDE4 B inhibitor is initiated at least six weeks following the brain injury.9. The method of claim 8 , wherein administration of the selective PDE4 B inhibitor is initiated at least six months following the brain injury.10. The method of claim 1 , wherein the selective PDE4 B inhibitor is administered for at least 2 weeks.11. The method of claim 1 , wherein Rand Rare each C-Calkyl.12. The method of claim 11 , wherein Ris Me and Ris Et.13. The method of claim 1 , wherein n is 0.14. The method of claim 1 , wherein n is 1.15. The method of claim 1 , wherein Ar is optionally substituted phenyl.16. The method of claim 1 , wherein Ar is optionally substituted thiophenyl.17. The method of claim 16 , wherein the thiophenyl is substituted with one or more of Cl claim 16 , F claim 16 , CH claim 16 , and SCH.20. The method of claim 1 , wherein the subject is human.22. (canceled)23. The method of claim 21 , wherein the improvement ...

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Номер записи: 84
16-02-2017 дата публикации

Pyrimidine Compounds and Use as Anti-Cervical Cancer Thereof

Номер: US20170044110A1
Автор: CHEN Qianming, He Yang, Jiang Lu, ZHAO Hang
Принадлежит:

Provided is use of a pyrimidine compound or a pharmaceutically acceptable salt thereof in preparation of an anti-cervical cancer medicament. Research of the present invention has found that the above-mentioned pyrimidine compound can be effective against cervical cancer, and has a good inhibition effect on E6 and E7 of HPV16, and indicates that the above-mentioned pyrimidine compound also has a good anti-human papilloma virus effect, providing a new choice for clinical medication. 2. The medicament according to claim 1 , characterized in that said cervical cancer is in presence of an infection by human papilloma virus.3. The medicament according to claim 2 , characterized in that said cervical cancer is caused by human papilloma virus.4. (canceled)5. The medicament according to claim 3 , characterized in that said human papilloma virus is HPV16 claim 3 , HPV18 claim 3 , HPV31 or HPV33.6. (canceled)7. The medicament according to claim 1 , characterized in that said medicament is an inhibitor of E6 and/or E7 proteins in HPV16.8. The medicament according to claim 1 , characterized in that R is chosen from substituted or unsubstituted C4-6 aryl or heterocyclic aryl claim 1 , in which claim 1 , said heterocyclic aryl is an oxygenousor nitrogenous group.9. The medicament according to claim 1 , characterized in that said substituents are chosen from C1-4 alkyl claim 1 , C1-2 alkoxyl claim 1 , C1-2 aminoalkyl claim 1 , amino claim 1 , or halogens.11. The pyrimidine compound according to claim 10 , characterized in that Rto Rare chosen from C1-4 alkyl claim 10 , C1-2alkoxyl claim 10 , C1-2aminoalkyl claim 10 , amino or H.12. The pyrimidine compound according to claim 11 , characterized in that Rto Rare chosen from C1-4 alkyl or C1-2alkoxyl.13. The pyrimidine compound according to claim 12 , characterized in that Rand Rare H; Rand Rare chosen from H or C1-2 alkoxyl with the proviso that Rand Rare not simultaneously H; and Ris C1-4 alkyl.14. The pyrimidine compound according ...

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Номер записи: 85
19-02-2015 дата публикации

SUBSTITUTED PYRAZINO[2,3-D]ISOOXAZOLES AS INTERMEDIATES FOR THE SYNTHESIS OF SUBSTITUTED PYRAZINECARBOXAMIDES

Номер: US20150051396A1
Автор: HANAKI Naoyuki, Murakami Takeshi, NAITOU Hiroyuki, NAKAMURA Kouki, WATANABE Katsuyuki
Принадлежит:

The object of the present invention is to provide a compound which is useful as a production intermediate of pyrazine carboxamide derivative such as 6-fluoro-3-hydroxy-2-pyrazine carboxamide. The present invention provides a pyrazino[2,3-d]isoxazole derivative represented by the formula (I): 3. The production method according to claim 1 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents an optionally substituted alkoxy group.4. The production method according to claim 2 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents an optionally substituted alkoxy group.5. The production method according to claim 1 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents a methoxy group claim 1 , an ethoxy group claim 1 , an n-propoxy group claim 1 , an isopropoxy group claim 1 , or an n-butoxy group.6. The production method according to claim 2 , wherein X represents a fluorine atom and Y represents —C(═O)R where R represents a methoxy group claim 2 , an ethoxy group claim 2 , an n-propoxy group claim 2 , an isopropoxy group claim 2 , or an n-butoxy group. This is a divisional of U.S. patent application Ser. No. 13/886,483, filed May 3, 2013, which is a Continuation Application of PCT/JP2011/076029, filed on Nov. 11, 2011, which is based on and claims priority under 35 USC 119 from Japanese Patent Application Nos. 2010-253414 filed on Nov. 12, 2010, 2010-256510 filed on Nov. 17, 2010, and 2011-025760 filed on Feb. 9, 2011. The entire disclosures of the prior applications are considered part of the disclosure of the accompanying divisional application, and are hereby incorporated by reference.1. Technical FieldThe present invention relates to a pyrazino[2,3-d]isoxazole derivative that is useful as a production intermediate or the like of 6-fluoro-3-hydroxy-2-pyrazine carboxamide (hereinafter referred to as “T-705”) useful for treatment such as prevention and therapy of influenza virus ...

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Номер записи: 86
19-02-2015 дата публикации

PYRAZINO[2,3-b]PYRAZINE mTOR KINASE INHIBITORS FOR ONCOLOGY INDICATIONS AND DISEASES ASSOCIATED WITH THE mTOR/PI3K/AKT PATHWAY

Номер: US20150051397A1
Автор: Elsner Jan, Harris Roy L., Lee Branden, Mortensen Deborah, Packard Garrick, Papa Patrick, PARNES Jason, Perrin-Ninkovic Sophie, Riggs Jennifer, Sapienza John, SHEVLIN Graziella I., TEHRANI Lida, Zhao Jingjing
Принадлежит:

Provided herein are Heteroaryl Compounds having the following structure: 120-. (canceled)22. The compound of claim 21 , wherein the compound is 2-bromo-N-(3 claim 21 ,5-dibromopyrazin-2-yl)acetamide.23. The compound of claim 21 , wherein the compound is 2-chloro-N-(3 claim 21 ,5-dibromopyrazin-2-yl)acetamide.24. The compound of claim 21 , wherein the compound is N-(3 claim 21 ,5-dibromopyrazin-2-yl)-2-iodoacetamide.26. The compound of claim 25 , wherein the compound is N-(3 claim 25 ,5-dibromopyrazin-2-yl)-2-methyl-2-(2-(tetrahydro-2H-pyran-4-yl)ethylamino)propanamide.27. The compound of claim 25 , wherein the compound is 1-amino-N-(3 claim 25 ,5-dibromopyrazin-2-yl)cyclopropanecarboxamide.29. The compound of claim 28 , wherein the compound is ethyl 2-(5-bromo-3-(isopropylamino)pyrazin-2-ylamino)acetate.30. The compound of claim 28 , wherein the compound is ethyl 2-(5-bromo-3-(2 claim 28 ,4-dimethoxybenzylamino)pyrazin-2-ylamino)acetate.31. The compound of claim 28 , wherein the compound is ethyl 2-(5-bromo-3-(trans-4-methoxycyclohexylamino)pyrazin-2-ylamino)acetate.32. The compound of claim 28 , wherein the compound is ethyl 2-(5-bromo-3-(2-(tetrahydro-2H-pyran-4-yl)ethylamino)pyrazin-2-ylamino)acetate.34. The compound of claim 33 , wherein the compound is ethyl 2-(3 claim 33 ,5-dibromopyrazin-2-ylamino)acetate. This application is a divisional of U.S. application Ser. No. 13/927,255, filed Jun. 26, 2013, currently allowed, which is a continuation of U.S. application Ser. No. 13/295,513, filed Nov. 14, 2011, now U.S. Pat. No. 8,507,492, issued Aug. 13, 2013, which is a continuation of U.S. application Ser. No. 12/605,791, filed Oct. 26, 2009, now U.S. Pat. No. 8,110,578, issued Feb. 7, 2012, which claims the benefit of U.S. Provisional Application No. 61/108,627, filed Oct. 27, 2008, the entire contents of each of which are incorporated herein by reference.Provided herein are certain heteroaryl compounds, compositions comprising an effective amount of one or more ...

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Номер записи: 87
03-03-2022 дата публикации

AMINOCARBAMOYL COMPOUNDS FOR THE TREATMENT OF VIRAL INFECTIONS

Номер: US20220064128A1
Автор: CHEN Jianguo, Liang Chungen, Miao Kun, Wu Yao, Yun Hongying, ZHANG WEIXING
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to compounds of formula (I),

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Номер записи: 88
25-02-2021 дата публикации

SUBSTITUTED THIAZOLO-PYRIDINE COMPOUNDS AS MALT1 INHIBITORS

Номер: US20210052556A1
Автор: Deshmukh Gokul Keruji, Irlapati Nageswara Rao, Jagdale Arun Rangnath, Kamboj Rajender Kumar, Kukreja Gagan, Kulkarni Kiran Chandrashekhar, PALLE Venkata P., Sinha Neelima, Vyavahare Vinod Popatrao
Принадлежит:

Disclosed are compounds of the general formula (I), 2. The compound of formula (I) claim 1 , a tautomer thereof claim 1 , a stereoisomer thereof claim 1 , a polymorph thereof claim 1 , a solvate thereof claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , wherein Ris selected from hydrogen and substituted or unsubstituted alkyl.3. The compound of formula (I) claim 1 , a tautomer thereof claim 1 , a stereoisomer thereof claim 1 , a polymorph thereof claim 1 , a solvate thereof claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , wherein Ris selected from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , and —CF.4. The compound of formula (I) claim 1 , a tautomer thereof claim 1 , a stereoisomer thereof claim 1 , a polymorph thereof claim 1 , a solvate thereof claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , wherein Ris selected from{'sup': 4', '5', '5a, 'a) alkyl or alkyl substituted with 1 to 4 substituents independently selected from halogen, cycloalkyl, substituted or unsubstituted heterocyclyl, —OR, —NRR, and substituted or unsubstituted aryl,'}b) cycloalkyl or cycloalkyl substituted with substituted or unsubstituted alkyl,c) cycloalkenyl,d) substituted or unsubstituted aryl,e) substituted or unsubstituted heteroaryl,{'sup': '4', 'f) heterocyclyl or heterocyclyl substituted on ring carbon atom with 1 to 2 substituents independently selected from halogen, —OR, and substituted or unsubstituted alkyl, and'}{'sup': a', 'b', 'a', 'b', '4, 'g) —NRR, wherein Rand Rare independent selected from cycloalkyl and alkyl or alkyl substituted with 1 to 2 substituents independently selected from cycloalkyl, OR, and substituted or unsubstituted aryl.'}8. The compound of formula (I) claim 1 , a tautomer thereof claim 1 , a stereoisomer thereof claim 1 , a polymorph thereof claim 1 , a solvate thereof claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , ...

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Номер записи: 89
08-05-2014 дата публикации

CRYSTALS OF GLYCINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF

Номер: US20140128605A1
Автор: Nogami Tsutomu, Shiraki Motohiro, Takahashi Hirozumi
Принадлежит: Toray Industries, Inc.

A crystal of (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid has excellent chemical and physical stability, and a medical use thereof. 1. A crystal of (S ,E)-2-(2 ,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid.2. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 17.1 claim 1 , 17.7 claim 1 , 18.7 claim 1 , 19.9 and 21.0° in powder X-ray diffraction.3. The crystal according to claim 2 , which exhibits an endothermic peak in the range of 178 to 182° C. in thermogravimetric-differential thermal analysis.4. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 5.9 claim 1 , 8.3 claim 1 , 11.8 claim 1 , 13.2 and 21.7° in powder X-ray diffraction.5. The crystal according to claim 4 , which exhibits an endothermic peak in the range of 167 to 171° C. in thermogravimetric-differential thermal analysis.6. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 6.6 claim 1 , 8.3 claim 1 , 11.1 claim 1 , 14.6 and 18.2° in powder X-ray diffraction.7. The crystal according to claim 6 , which exhibits an endothermic peak in the range of 100 to 104° C. in thermogravimetric-differential thermal analysis.8. The crystal according to claim 1 , which is a non-solvate or a hydrate.9. A pharmaceutical comprising as an effective component said crystal according to .10. A therapeutic or prophylactic agent for inflammatory bowel disease claim 1 , allergic dermatitis claim 1 , multiple sclerosis or leukemia claim 1 , comprising as an effective component said crystal according to . This disclosure relates to a crystal of glycine derivative and a medical use thereof.Pharmaceuticals are required to maintain the quality thereof for a long time during distribution, storage and the like, and high chemical and physical stability is demanded for compounds as effective components. Thus, for the effective components of pharmaceuticals, crystals which are expected to have high ...

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Номер записи: 90
10-03-2022 дата публикации

Chemical Compound Manufacture, New Salt Form, And Therapeutic Uses Thereof

Номер: US20220073467A1
Автор: Liakatos Angela
Принадлежит: EUSTRALIS PHARMACEUTICALS LIMITED (Trading as Pressura Neuro)

There is disclosed a method of preparing a compound of Formula (1), or a salt thereof (1) the method comprising: a) treating a compound of Formula (2) sequentially with o-tolylmagnesium chloride, N-methylpiperazine and iodine, under conditions sufficient to obtain a compound of Formula (3) b) treating the compound of Formula (3) from step a) with 3,5-bis(trifluoromethyl)benzyl bromide and a suitable base, under conditions sufficient to obtain a compound of Formula (1). 3. A method according to claim 1 , wherein step (a) is conducted in THF claim 1 , and preferably Formula (2) is added to 1M o-tolylmagnesium chloride in THF at about 0° C.4. A method according to claim 1 , wherein Formula (2) is added to 1M o-tolylmagnesium chloride in THF at about 0° C. claim 1 , preferably over about 1 hr claim 1 , and the reaction is warmed to about 20° C.5. A method according to claim 1 , wherein N-methylpiperazine is added at about 20° C.6. A method according to claim 1 , wherein about 5 M equivalents of N-methylpiperazine is added claim 1 , preferably in one portion.7. A method according to claim 6 , wherein the reaction mixture is cooled claim 6 , preferably to about 5° C. claim 6 , after the reaction mixture is stirred for at least 10 hours at about 20° C.8. A method according to claim 7 , wherein to the cooled reaction mixture is added AcOH claim 7 , preferably about 7% AcOH in water.9. A method according to claim 1 , wherein iodine is subsequently reacted as a THF solution claim 1 , preferably about 1.5 mol equivalents claim 1 , preferably under nitrogen at about 0° C.10. A method according to claim 1 , wherein the base of step b) is potassium tert-butoxide claim 1 , preferably in an amount of about 1.5 mol equivalents relative to Formula (3).11. A method according to claim 1 , wherein 3 claim 1 ,5-Bis(trifluoromethyl)benzyl bromide is reacted with Formula (3) at about 1.2 mol equivalent.12. A method according to claim 1 , wherein the compound of Formula (3) is purified by a ...

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Номер записи: 91
15-05-2014 дата публикации

SUBSTITUTED 3-HETEROAROYLAMINO-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS

Номер: US20140135328A1
Автор: BUNING Christian, RUF Sven, SADOWSKI Thorsten, SCHREUDER Herman, WIRTH Klaus
Принадлежит: SANOFI

The present invention relates to compounds of the formula I, 9. A compound of the formula I claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , selected from:(S)-3-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid3-Biphenyl-4-yl-3-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-propionic acid(S)-3-[(6-Methylamino-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(5-Methyl-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(6-Chloro-pyrazine-2-carbonyl)-amino]-3-o-tolyl-propionic acid3-(2-Chloro-phenyl)-3-[(pyrazine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(5-methyl-pyrazine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(6-methylamino-pyrazine-2-carbonyl)-amino]-propionic acid(S)-3-[(2,6-Dimethoxy-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2,6-Bis-dimethylamino-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(4,6-Dimethoxy-pyrimidine-2-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2-Amino-6-isobutyl-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid(S)-3-[(2,6-Dimethyl-pyrimidine-4-carbonyl)-amino]-3-o-tolyl-propionic acid3-[(2-Amino-6-isopropyl-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid3-(2-Chloro-phenyl)-3-[(4,6-dimethoxy-pyrimidine-2-carbonyl)-amino]-propionic acid3-(2-Chloro-phenyl)-3-[(2,6-dimethoxy-pyrimidine-4-carbonyl)-amino]-propionic acid3-[(2-Amino-6-isobutyl-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid3-[(2,6-Bis-dimethylamino-pyrimidine-4-carbonyl)-amino]-3-(2-chloro-phenyl)-propionic acid and3-(2-Chloro-phenyl)-3-[(6-phenyl-2-piperidin-1-yl-pyrimidine-4-carbonyl)-amino]-propionic acid.11. A pharmaceutical composition comprising the compound of or a physiologically acceptable salt thereof or a physiologically acceptable solvate of any of them.12. The pharmaceutical composition of claim 11 , further ...

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Номер записи: 92
15-05-2014 дата публикации

ISOXAZOLINE-SUBSTITUTED BENZAMIDE COMPOUND AND PESTICIDE

Номер: US20140135496A1
Автор: FURUKAWA Yuki, Ikeda Eitatsu, KOMODA Mitsuaki, MASUZAWA Yoshihide, MITA Takeshi, Toyama Ken-ichi, YAOSAKA Manabu
Принадлежит: NISSAN CHEMICAL INDUSTRIES, LTD.

An isoxazoline-substituted benzamide compound of formula (1) or a salt thereof: 117-. (canceled)19. 4-Hydroxyiminomethyl substituted benzamide compound or the salt thereof according to claim 18 , wherein{'sup': '1', 'Ais carbon atom,'}W is oxygen atom,{'sub': 1', '6', '1', '6, 'sup': 5', '7', '6, 'Y is halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl, —ORor —N(R)R,'}{'sup': 1', '1a, 'Ris —CH═NOR,'}{'sup': '1a', 'sub': 1', '6, 'Ris C-Calkyl,'}{'sup': 2', '14a, 'sub': 2', '3', '6', '1', '6, 'Ris hydrogen atom, —CHR, C-Calkynyl or C-Calkoxycarbonyl,'}{'sup': '5', 'sub': 1', '6', '1', '6, 'Ris C-Calkyl or C-Chaloalkyl,'}{'sup': '6', 'sub': 1', '6', '1', '6, 'Ris —CHO, C-Calkylcarbonyl or C-Calkoxycarbonyl,'}{'sup': 14a', '25, 'Ris cyano or —OR,'}{'sup': 25', '32, 'sub': 1', '4', '1', '4, 'Ris C-Calkyl, C-Chaloalkyl or —C(O)OR, and'}{'sup': '32', 'sub': 1', '6, 'Ris C-Calkyl.'}20. 4-Hydroxyiminomethyl substituted benzamide compound or the salt thereof according to claim 18 , wherein{'sup': '1', 'Ais carbon atom,'}W is oxygen atom,{'sub': 1', '6', '1', '6, 'sup': 5', '7', '6, 'Y is halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl, —ORor —N(R)R,'}{'sup': 1', '1c, 'Ris —C(O)OR,'}{'sup': '1c', 'sub': 1', '6', '3', '6, 'Ris C-Calkyl or C-Ccycloalkyl,'}{'sup': 2', '14a', '5, 'sub': 1', '6', '2', '1', '6', '1', '6', '1', '6, 'Ris hydrogen atom, C-Calkyl, —CHR, E-5, —C(O)R, C-Calkoxycarbonyl, C-Chaloalkoxycarbonyl or C-Chaloalkylthio,'}{'sup': '5', 'sub': 1', '6', '1', '6, 'Ris C-Calkyl or C-Chaloalkyl,'}{'sup': '6', 'sub': 1', '6', '1', '6, 'Ris —CHO, C-Calkylcarbonyl or C-Calkoxycarbonyl,'}{'sup': 14a', '25', '32, 'Ris cyano, —OR, or —NHC(O)OR,'}{'sup': '15', 'sub': 1', '6', '1', '6', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6, 'Ris C-Calkyl, C-Chaloalkyl, C-Calkoxy C-Calkyl, C-Calkylthio C-Calkyl or C-Ccycloalkyl,'}{'sup': 25', '32, 'sub': 1', '4', '1', '4, 'Ris C-Calkyl, C-Chaloalkyl or —C(O)OR,'}{'sup': '32', 'sub': 1', '6, 'Ris C-Calkyl,'}n is an integer of 0 or 1 ...

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Номер записи: 93
01-03-2018 дата публикации

NOVEL GLUTAMINASE INHIBITORS

Номер: US20180057487A1
Автор: Babu Govindarajulu, Bhavar Prashant K, Merikapudi Gayatri Swaroop, Vakkalanka Swaroop K., Viswanadha Srikant
Принадлежит:

The present disclosure provides compounds of formula (I) to (III) as glutaminase inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of diseases or disorders involving glutamine. 9. (canceled)10. A compound of claim 1 , wherein P and Q are each independently selected from —NRC(═O)—(CRR)— claim 1 , —(CRR)—C(═O)—NR— claim 1 , —NRC(═O)— or —NR— claim 1 , wherein Rand Rare independently selected from hydrogen claim 1 , substituted or unsubstituted Calkyl claim 1 , halogen claim 1 , hydroxy and substituted or unsubstituted Calkoxy.11. A compound of claim 1 , wherein P and Q are each independently selected from —NH—C(═O)—(CRR)— claim 1 , —(CRR)—C(═O)—NH— claim 1 , —NH—C(═O)— or —NH— claim 1 , wherein Rand Rare hydrogen.12. A compound of claim 1 , wherein{'sub': 2', '2, '(i) each of P and Q are independently —NH—C(═O)—(CH)—, —(CH)—C(═O)—NH—, —NH—C(═O)— or —NH—;'}{'sub': 2', '2, '(ii) P is —(CH)—C(═O)—NH— and Q is —NH—C(═O)—CH—, —NH—C(═O)— or —NH—;'}{'sub': 2', '2, '(iii) P is —(CH)—C(═O)—NH—, —NH—C(═O)— or —NH— and Q is —NH—C(═O)—CH—; or'}{'sub': 2', '2, '(iv) P is —(CH)—C(═O)—NH— and Q is —NH—C(═O)—CH—.'}13. A compound of claim 1 , wherein both P and Q are independently selected from —NH—C(═O)—CH— or —CH—C(═O)—NH—.15. A compound of claim 1 , wherein{'sub': 1', '1-6', '1-3, 'sup': x', 'x, 'Lis absent, substituted or unsubstituted Calkyl or NR, wherein Ris hydrogen or Calkyl;'}{'sub': '2', 'Lis substituted or unsubstituted 3 to 10 membered heterocyclyl; and'}{'sub': 3', '1-6', '1-3, 'sup': x', 'x, 'Lis absent, substituted or unsubstituted Calkyl or NR, wherein Ris hydrogen or Calkyl.'}16. A compound of claim 1 , wherein{'sub': 1', '1-6, 'Lis absent or substituted or unsubstituted Calkyl;'}{'sub': '2', 'Lis substituted or unsubstituted 3 to 10 membered heterocyclyl; and'}{'sub': 3', '1-6, 'Lis absent or substituted or unsubstituted Calkyl.'}17. (canceled)18. (canceled)19. A compound of ...

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Номер записи: 94
17-03-2022 дата публикации

Methods and compositions for treatment of pulmonary hypertension and other lung disorders

Номер: US20220079949A1
Автор: Adaani FROST, Alain Romero, Hugh Smyth, Jeffry Weers, Martin Donovan, Revati Shreeniwas, Robert Curtis, Zhen Xu
Принадлежит: Respira Therapeutics Inc

Provided herein are methods for treating pulmonary hypertension. The methods include administering to a subject in need thereof an effective amount of a vasodilator, wherein the vasodilator is administered to the subject via inhalation pro re nata using a portable inhaler. In some embodiments, the vasodilator is a PDE5 inhibitor. Pharmaceutical compositions for pro re nata administration of vasodilators are also described.

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Номер записи: 95
22-05-2014 дата публикации

REVERSE AMIDE COMPOUNDS AS PROTEIN DEACETYLASE INHIBITORS AND METHODS OF USE THEREOF

Номер: US20140142117A1
Автор: Bradner James E., Huang Guoxiang, Mazitschek Ralph, Ogier Walter, van Duzer John H., Xie Dejian, Yu Nan
Принадлежит:

The present invention relates to novel “reverse amide” compounds comprising a zinc chelator group, and the use of such compounds in the inhibition of HDAC6 and in the treatment of various diseases, disorders or conditions related to HDAC6. 121-. (canceled)23. The compound of claim 22 , wherein ring A is phenyl claim 22 , naphthyl claim 22 , anthracenyl claim 22 , pyridinyl claim 22 , pyrimidinyl claim 22 , pyrazinyl claim 22 , indolyl claim 22 , imidazolyl claim 22 , oxazolyl claim 22 , furyl claim 22 , thienyl claim 22 , thiazolyl claim 22 , triazolyl claim 22 , isoxazolyl claim 22 , quinolinyl claim 22 , pyrrolyl claim 22 , pyrazolyl claim 22 , or 5 claim 22 ,6 claim 22 ,7 claim 22 ,8-tetrahydroisoquinoline; each of which may be optionally substituted with halo.24. The compound of claim 22 , wherein Ris H claim 22 , methyl claim 22 , ethyl claim 22 , propyl claim 22 , i-propyl claim 22 , butyl claim 22 , i-butyl claim 22 , t-butyl claim 22 , pentyl claim 22 , hexyl claim 22 , phenyl claim 22 , naphthyl claim 22 , pyridinyl claim 22 , OH or OCH; each of which may be optionally substituted with OH claim 22 , halo claim 22 , alkyl claim 22 , or alkoxy.25. The compound of claim 22 , wherein the carbonyl and the Z group attached to ring A are disposed para to each other.26. The compound of claim 22 , wherein the carbonyl and Z group attached to ring A are disposed meta to each other.27. The compound of claim 22 , wherein the carbonyl and the Z group attached to ring A are disposed ortho to each other.29. The compound of claim 28 , wherein ring B is phenyl claim 28 , pyridinyl claim 28 , pyrimidinyl claim 28 , or pyrazinyl; wherein phenyl claim 28 , pyridinyl claim 28 , pyrimidinyl claim 28 , or pyrazinyl may be optionally substituted with alkyl claim 28 , aryl claim 28 , heteroaryl claim 28 , cycloalkyl claim 28 , heterocycloalkyl claim 28 , aralkyl claim 28 , haloalkyl claim 28 , halo claim 28 , OH claim 28 , NH claim 28 , NHR″ claim 28 , CN claim 28 , N claim 28 , or ...

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Номер записи: 96
09-03-2017 дата публикации

1,2-SUBSTITUTED CYCLOPENTANES AS OREXIN RECEPTOR ANTAGONISTS

Номер: US20170066744A1
Автор: Fieldhouse Charlotte, FUJIMOTO Tatsuhiko, Glen Angela, Maine Stephanie, Robinson John Stephen
Принадлежит:

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, (I) wherein L, X, R, R, R, Rand Rare as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. 116.-. (canceled)18. A compound according to claim 17 , wherein Rrepresents a 5- or 6-membered heteroaryl group containing one or two ring heteroatoms independently selected from nitrogen claim 17 , oxygen and sulphur claim 17 , the heteroaryl group being optionally substituted by one or two substituents independently selected from halogen claim 17 , C-Calkyl and C-Chaloalkyl.191. A compound according to claim 17 , wherein Rrepresents a 5- or 6-membered heteroaryl group selected from pyridinyl claim 17 , pyrimidinyl and pyrazinyl claim 17 , all optionally substituted as claimed in claim .20. A compound according to claim 19 , wherein Rrepresents a group selected from:(i) 4-(trifluoromethyl)pyridin-2-yl,(ii) 5-(trifluoromethyl)pyridin-2-yl,(iii) 5-(trifluoromethoxy)pyridin-2-yl,(iv) 6-(trifluoromethyl)pyridin-2-yl,(v) 6-(trifluoromethyl)pyridin-3-yl,(vi) 5-chloropyridin-2-yl,(vii) 5-bromopyridin-2-yl,(viii) 3-fluoro-5-(trifluoromethyl)pyridin-2-yl,(ix) 3-chloro-5-(trifluoromethyl)pyridin-2-yl,(x) 3-bromo-5-(trifluoromethyl)pyridin-2-yl,(xi) 5-bromo-3-methoxypyridin-2-yl,(xii) 3-methyl-5-(trifluoromethyl)pyridin-2-yl,(xiii) 5-(trifluoromethyl)pyrimidin-2-yl,(xiv) 5-ethylpyrimidin-2-yl,(xv) 5-(trifluoromethyl)pyrazin-2-yl,(xvi) 5-chloropyrazin-2-yl,(xvii) 5-(ethyl)pyrazin-2-yl,(xviii) 5-(cyclopropyl)pyrazin-2-yl,(xix) 5-(isopropyl)pyrazin-2-yl,(xx) 3-methyl-5-(trifluoromethyl)pyrazin-2-yl,(xxi) 3-ethyl-5-(trifluoromethyl)pyrazin-2-yl,(xxii) 3-cyclopropyl-5-(trifluoromethyl)pyrazin-2-yl, and(xxiii) 3-isopropyl-5-(trifluoromethyl)pyrazin-2-yl.21. A compound according to claim 17 , wherein X represents CH.22. A compound according to claim 17 , wherein L represents NH.23. A compound according to claim ...

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Номер записи: 97
29-05-2014 дата публикации

SUBSTITUTED AMINO-ACRYLCARBOXAMIDES AS KCNQ2/3 MODULATORS

Номер: US20140148454A1
Автор: Bahrenberg Gregor, Kühnert Sven, LUCAS Simon, Schröder Wolfgang
Принадлежит: Grünenthal GmbH

The invention relates to amino-arylcarboxamides, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders. 5. The compound according to claim 1 , wherein{'sup': '5', 'sub': 3', '3', '2', '3, 'Rdenotes F, Cl, CH, OCHor CHCH; and/or'}{'sup': '6', 'Rdenotes H; and/or'}{'sup': '7', 'sub': 3', '2', '3, 'Rdenotes CH, CHCHor cyclopropyl; and/or'}{'sup': '8', 'Rdenotes H.'}7. The compound according to claim 6 , whereinm denotes 1 or 2,{'sup': 1a', '1b, 'Rand Rrepresent H,'}{'sup': '1c', 'sub': 1-4', '1-4', '3', '1-4, 'Rdenotes C-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C-aliphatic residue, CFand C-aliphatic residue,'}or{'sub': 3-10', '1-4', '3', '1-4, 'denotes C-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C-aliphatic residue, CFand C-aliphatic residue,'}orm denotes 0 and{'sup': '1c', 'sub': 1-4', '3', '3', '1-4', '3', '2', '5', '3', '2', '5', '3-6, 'claim-text': [{'sub': 1-4', '3', '3', '1-4', '3', '2', '5', '3', '2', '5, 'wherein benzyl, phenyl, thienyl and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C-aliphatic residue, OCF, CF, CN, C-aliphatic residue, C(═O)CH, C(═O)CH, C(═O)OCHand C(═O)OCH, and'}, {'sub': 3-6', '1-4', '3', '3', '1-4, 'wherein the C-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C-aliphatic residue, OCF, CFC-aliphatic residue and C(═O)OH.'}], 'Rdenotes aryl or heteroaryl ...

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Номер записи: 98
29-05-2014 дата публикации

HETEROCYCLIC COMPOUNDS AND THEIR USE AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS

Номер: US20140148458A1
Автор: Bakker Margaretha Henrica Maria, Stewart Kent D., Turner Sean Colm
Принадлежит:

The present invention relates to a heterocyclic compound of the general formula (I) and their use and preparation, methods of making the compounds, compositions containing at least one of said compounds, and methods of treatment using at least one compound. In particular, compounds of the general formula (I) are useful for inhibiting glycogen synthase kinase 3 (GSK-3), 3. A heterocyclic compound of the general formula I as claimed in or , wherein at least one of the moieties Y , Y , Yand Yis N.4. A heterocyclic compound of the general formula I as claimed in claim 3 , wherein at least Yof the moieties Y claim 3 , Y claim 3 , Yand Yis N.5. A heterocyclic compound of the general formula I as claimed in wherein Yis N and the moieties Y claim 4 , Yand Yare CH or CR.20. A pharmaceutical composition comprising at least one compound of the formula I according to wherein A claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , m claim 4 , n claim 4 , o claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , and Yhave the same meaning as defined in any one of to claim 4 , the stereoisomers claim 4 , prodrugs and/or physiologically tolerated acid addition salts thereof claim 4 , optionally together with at least one physiologically acceptable carrier and/or auxiliary substance.21. A method for treating a medical disorder susceptible to treatment with a compound that modulates glycogen synthase kinase 3β activity claim 4 , said method comprising administering an effective amount of at least one compound of the formula I according to wherein A claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , m claim 4 , n claim 4 , o claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , X claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , and Yhave the same meaning as defined in any one of to claim 4 , the stereoisomers claim 4 , prodrugs and/or physiologically tolerated acid addition ...

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Номер записи: 99
29-05-2014 дата публикации

SPECIFIC CARBOXAMIDES AS KCNQ2/3 MODULATORS

Номер: US20140148468A1
Автор: Bahrenberg Gregor, Kühnert Sven, LUCAS Simon, Schröder Wolfgang
Принадлежит: Grünenthal GmbH

The invention relates to specific carboxamides, to processes for their preparation, to medicaments comprising these compounds and to the use of these compounds in the preparation of medicaments. 3. The compound according to claim 1 , wherein{'sup': '1', 'Arepresents S; and'}{'sup': 2', '12', '13, 'sub': '2', 'claim-text': {'sup': 12', '13, 'wherein Rand Rboth represent H or both represent F.'}, 'Arepresents S, S(═O)or CRR,'}4. The compound according to claim 1 ,wherein{'sup': 3', '7', '4', '7', '5', '7', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents CRand Arepresents CR; or'}{'sup': 3', '4', '7', '5', '7', '6', '7, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents CRand Arepresents CR; or'}{'sup': 3', '7', '4', '5', '7', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents CRand Arepresents CR; or'}{'sup': 3', '7', '4', '7', '5', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents N and Arepresents CR; or'}{'sup': 3', '4', '5', '7', '6', '7, 'n denotes 1 and Arepresents N, Arepresents N, Arepresents CRand Arepresents CR; or'}{'sup': 3', '4', '7', '5', '6', '7, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents N and Arepresents CR; or'}{'sup': 3', '4', '7', '5', '7', '6, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents CRand Arepresents N; or'}{'sup': 3', '7', '4', '5', '7', '6, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents CRand Arepresents N; or'}{'sup': 3', '7', '4', '5', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents N and Arepresents CR; or'}{'sup': 3', '7', '4', '7', '5', '6, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents N and Arepresents N; or'}{'sup': 3', '4', '7', '5', '7, 'n denotes 0 and Arepresents S, Arepresents CRand Arepresents CR;'}or{'sup': 3', '4', '7', '5, 'n denotes 0 and Arepresents S, Arepresents CRand Arepresents N;'}or{'sup': 3', '4', '7', '5', '7, 'n denotes 0 and Arepresents O, Arepresents CRand ...

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Номер записи: 100