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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 21782. Отображено 100.
29-03-2012 дата публикации

Substituted Pyrazine (Thio)Pyrans with a Herbicidal Action

Номер: US20120077678A1
Автор: Anja Simon, Anna Aleksandra Michrowska, Bernd Sievernich, Dschun Song, Frank Stelzer, Johannes Hutzler, Julia Major, Klaus Grossmann, Klaus Kreuz, Liliana Parra Rapado, Matthias Witschel, Ricarda Niggeweg, Tao QU, Thomas Ehrhardt, Thomas Seitz, Trevor William Newton, William Karl Moberg
Принадлежит: BASF SE

Substituted pyrazines of the formula I in which the variables are defined according to the description, their agriculturally suitable salts, processes and intermediates for preparing the pyrazines of the formula I, compositions comprising them and their use as herbicides, i.e. for controlling harmful plants, and also a method for controlling unwanted vegetation which comprises allowing a herbicidally effective amount of at least one pyrazine compound of the formula I to act on plants, their seed and/or their habitat.

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Номер записи: 1
26-07-2012 дата публикации

Process for the preparation of antibiotic compounds

Номер: US20120190842A1
Автор: Shiuan-Ting Chuang, Wei-Hong Tseng, Wen-Hsin Chang
Принадлежит: Savior Lifetec Corp

The present invention relates to a process for the preparation of carbapenem antibiotic compounds, which is useful for intravenous and intramuscular administration.

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Номер записи: 2
11-10-2012 дата публикации

Novel Process for the Preparation of Paliperidone

Номер: US20120259116A1
Автор: Dattatray Shamrao Metil, Dharmesh Kumar Arvindbhaipatel, Prashant Pandurangpawar, Praveen Raosaheb Supekar, Rajiv Kumar, Santosh Vitthal Pune
Принадлежит: Alkem Laboratories Ltd

The present invention relates to a novel process for the preparation of paliperidone by hydrolysis of 9 -O-acylated paliperidone. In a preferred embodiment of the present invention, Paliperidone Form (II) of purity of about 98 % or more was obtained by basic hydrolysis of 9-O-Acetyl Paliperidone.

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Номер записи: 3
01-11-2012 дата публикации

Polycyclic ring-fused compound and organic thin film transistor utilizing same

Номер: US20120273770A1
Автор: Hiroaki Nakamura, Hirofumi Kondo, Masahiro Kawamura, Masatoshi Saito, Misa Sunagawa, Naoki Kurihara
Принадлежит: Idemitsu Kosan Co Ltd

A compound for an organic thin film transistor represented by the following formula (1):

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Номер записи: 4
27-12-2012 дата публикации

Heterocyclic compound and organic light-emitting diode and flat display device including the heterocyclic compound

Номер: US20120326134A1
Автор: Hee-Joo Ko, Hye-jin Jung, Jin-O Lim, Jong-hyuk Lee, Sang-hyun Han, Seok-Hwan Hwang, Sun-Young Lee, Sung-Chul Kim, Yoon-Hyun Kwak, Young-Kook Kim
Принадлежит: Samsung Display Co Ltd

A heterocyclic compound, an organic light-emitting diode, and a flat display device, the heterocyclic compound being represented by Formula 1, below:

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Номер записи: 5
03-01-2013 дата публикации

Substituted Pyridazines Having Herbicidal Action

Номер: US20130005576A1
Автор: Andree Van Der Kloet, Anja Simon, Anna Aleksandra Michrowska-Pianowska, Dschun Song, Frank Stelzer, Hans Wolfgang Hoeffken, Helmut Kraus, Johannes Hutzler, Julia Major, Klaus Grossmann, Klaus Kreuz, Liliana Parra Rapado, Matthias Witschiel, Ruediger Reingruber, Tao QU, Thomas Ehrhardt, Thomas Mietzner, Thomas Seitz, Trevor William Newton, William Karl Moberg
Принадлежит: BASF SE

Substituted pyridazines of the formula I in which the variables are defined according to the description, processes and intermediates for preparing the compounds of the formula I and their N-oxides, their agriculturally suitable salts, compositions comprising them and their use as herbicides, and also methods for controlling unwanted vegetation.

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Номер записи: 6
14-03-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130065913A1
Автор: Blench Toby Jonathan, Capaldi Carmelida, Edwards Christine, Heald Robert Andrew, Kulagowski Janusz Jozef, SUTTON Jonathan Mark
Принадлежит: CHIESI FARMACEUTICI S.p.A.

Compounds of formula (I): 2. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein A is a group CH.3. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein Ris hydrogen or a —SOR claim 1 , wherein Ris (C-C)alkyl.4. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein Ris a group —C(O)—XR.5. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein X is —O— or —NH—.6. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein Ris:hydrogen;{'sub': 1', '6, '(C-C)alkyl; or'}{'sup': '1', 'a radical of formula -[Alk]-Z,'}{'sup': '1', 'sub': 1', '4, 'wherein Alkrepresents a (C-C)alkylene radical, and'}Z is:{'sub': 9', '10', '9', '10', '1', '6, '(i) —NRR, wherein Rand Rare independently hydrogen or optionally substituted (C-C)alkyl;'}or{'sup': '+', 'sub': 11', '12', '13', '11', '12', '13', '1', '6, '(ii) —NRRR, wherein R, Rand Rare each independently optionally substituted (C-C)alkyl.'}7. A compound claim 1 , pharmaceutically acceptable salt thereof claim 1 , or N-oxide thereof according to claim 1 , wherein Ris hydrogen claim 1 , (C-C)alkyl claim 1 , NRR(C-C)alkyl claim 1 , (C-C)alkenyl claim 1 , phenyl(C-C)alkyl claim 1 , wherein such phenyl ring is optionally substituted by a group —(C-C)alkylNRRor by a group —(C-C)alkylNRRR claim 1 , —(CH)CONRR claim 1 , —CH—(CH)NRSOR claim 1 , —(CH)—(CH)—SO(C-C)alkyl claim 1 , —(CH)SO(C-C)alkyl claim 1 , wherein such (C-C)alkyl is optionally substituted by a group —NRRor —NRRR claim 1 , —SO-phenyl claim 1 , wherein such phenyl ring is optionally substituted by a group —(C-C)alkylNRR claim 1 , and —(CH)W claim 1 , wherein W is a 5 or 6-membered heteroaryl ring claim 1 , which is optionally substituted by a ...

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Номер записи: 7
21-03-2013 дата публикации

Heterocyclic Compounds as Janus Kinase Inhibitors

Номер: US20130071415A1
Автор: Babu Yarlagadda S., Kotian Pravin L., Wu Minwan
Принадлежит: BioCryst Pharmaceuticals, Inc.

The invention provides compounds of formula I: 2. The compound of wherein X is CR.3. (canceled)4. The compound of wherein Ris H claim 2 , NO claim 2 , COH claim 2 , COCHCH claim 2 , —C(O)NH claim 2 , —C(O)NHNH claim 2 , —C(O)NHNHCOtBu claim 2 , —NHS(O)CH claim 2 , —NHCOCF claim 2 , —NHor —NHCHCOH.57-. (canceled)8. The compound of wherein Y is CR.9. (canceled)10. The compound of wherein Ris H claim 8 , NO claim 8 , COH claim 8 , —NHS(O)CH claim 8 , —NHCOCF claim 8 , —NHor —NHCHCOH.1113-. (canceled)14. The compound of wherein Z is CH.15. (canceled)16. (canceled)17. The compound of wherein V is CR.18. (canceled)19. The compound of wherein Ris H claim 17 , CN or —C(O)NRR.2022-. (canceled)23. The compound of wherein V is N.2429-. (canceled)30. The compound of wherein Y and Z are CH.31. (canceled)32. The compound of wherein Ris H claim 1 , —NH claim 1 , —NHC(O)OCH claim 1 , —NHCHC(O)OH claim 1 , —NHCHCHC(O)OH claim 1 , —NHCH(COH)CHOH claim 1 , —NHCH(COH) claim 1 , or —NHS(O)CH.3340-. (canceled)41. The compound of wherein W is pyrazolyl claim 1 , wherein pyrazolyl is optionally substituted with one or more Rgroups.42. (canceled)43. (canceled)45. The compound of wherein Ris absent H.4652-. (canceled)5461-. (canceled)64. (canceled)70. A The compound of claim 1 , selected from the group consisting of:3-cyclopentyl-3-(4-(pyrrolo[1,2-f][1,2,4]triazin-4-yl)-1H-pyrazol-1-yl)propanenitrile;4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)pyrrolo[1,2-f][1,2,4]triazine;4-(1H-pyrazol-4-yl)pyrrolo[1,2-f][1,2,4]triazine;4-(1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide;4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carbonitrile;4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide;4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide;4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-6-nitropyrrolo[1,2-b]pyridazine-3-carboxamide;4-(1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carbonitrile;4-(1-(2-cyano-1-cyclopentylethyl)-1H- ...

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Номер записи: 8
21-03-2013 дата публикации

TRISUBSTITUTED TRIAZOLOPYRIMIDINES FOR USE IN PLATELET AGGREGATION INHIBITION

Номер: US20130072503A1
Автор: Guile Simon, Hardern David, Ingall Anthony, Springthorpe Brian, Willis Paul
Принадлежит: AstraZeneca

The invention provides new triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation. 2. A compound according to in which Ris 3 claim 1 ,3 claim 1 ,3 claim 1 ,-trifluoropropyl claim 1 , butyl or propyl.3. A compound according to in which Ris phenyl or 4-fluorophenyl or 3 claim 1 ,4-difluorophenyl.4. A compound according to in which R is CHOH or OCHCHOH.5. A compound according to which is:[1R-[α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol:[1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;[1S-(1α,2α,3β(1S*,2R*),5]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;[1R-[1α,2α,3β(1R*,2S*),5p]]-3-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2-(4-fluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol;[1S-(1α,2α,3β(1S*,2R*),5β)]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;[1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2(3,4-difluorophenyl)cyclopropyl]-amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-triol;[1S-[1α,2α,3β(1S*,2R*),5]]-3-[5-(Butylthio)-7-[(2-phenylcylopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxethoxy)-cyclopentane-1,2-diol;or ...

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Номер записи: 9
28-03-2013 дата публикации

MEDICAMENTS CONTAINING VARDENAFIL HYDROCHLORIDE TRIHYDRATE

Номер: US20130078306A1
Автор: Bellinghausen Rainer, Grunenberg Alfons, Henck Jan-Olav, Ohm Andreas, Serno Peter, Vollers Elmer
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to a method for producing medicaments that contain vardenafil hydrochloride, essentially as trihydrate in solid form, and to medicaments that can be obtained according to this method 1. A method for producing medicaments comprising vardenafil hydrochloride trihydrate in solid form , characterized in thata) vardenafil hydrochloride with any water content is employed for producing the medicament,b) the verdenafil hydrochloride is converted substantially into the trihydrate form at an intermediate processing stage or in the final product.2. The method as claimed in claim 1 , characterized in that coated tablets are produced as medicament.3. The method as claimed in and claim 1 , characterized in that the intermediate processing stage or the final product claim 1 , or the coated tablet claim 1 , are brought into contact with moistened gas until the trihydrate has substantially formed.4. The method as claimed in claim 3 , characterized in that air is employed as gas.5. The method as claimed in and claim 3 , characterized in that the gas employed has a relative humidity of from 35% to 100%.65. A medicament obtainable by the method as claimed in at least one of to .7. A coated tablet obtainable by the method as claimed in to .8. A medicament as claimed in either of and for the treatment and/or prophylaxis of sexual dysfunctions.9. A medicament as claimed in either of and for the treatment and/or prophylaxis of erectile dysfunction.10. The use of a medicament as claimed in either of and for the treatment and/or prophylaxis of erectile dysfunction. The application relates to medicaments which comprise vardenafil hydrochloride substantially as trihydrate in solid form, and processes for the production thereof.The active pharmaceutical ingredient vardenafil (IUPAC name: 2-ethoxy-5-[(4-ethyl-1-piperazinyl)sulfonyl]phenyl}-5-methyl-7-propylimid-azo[5,1-f][1,2,4]triazin-4(3H)-one), vardenafil hydrochloride and vardenafil hydrochloride trihydrate and the use ...

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Номер записи: 10
28-03-2013 дата публикации

Substitute 2-amino-3-(Sulfony)pyrazol[1,5-a]pyramidines - serotonin 5-ht6 receptor antagonists, method for us thereof

Номер: US20130079350A1
Автор: Ivashchenko Andrey Alexandrovich, Ivashtchenko Alexander Vasilievich, Savchuk Nikolay Filippovich
Принадлежит:

The present invention relates to novel substituted 2-amino-3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1, to serotonin 5-HTreceptor antagonists, to novel drug substances and pharmaceutical compositions, to medicaments, methods for preparation thereof, and to methods for prophylaxis and treatment of various CNS diseases, pathogenesis of which is associated with disturbance of monoaminergic signaling pathways, more specifically over- or hypo-activation of serotonin 5-HTreceptors. 3. The method of claim 2 , wherein said compound is selected from the group claim 2 , consisting of: 5 claim 2 ,7-dimethyl-2-methylamino-3-(phenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-dimethylamino-3-(phenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-methylamino-3-(4-fluorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-dimethylamino-3-(4-fluorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-methylamino-3-(3-fluorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-dimethylamino-3-(3-fluorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , 5 claim 2 ,7-dimethyl-2-methylamino-3-(3-chlorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , and 5 claim 2 ,7-dimethyl-2-dimethylamino-3-(3-chlorophenylsulfonyl)pyrazolo[1 claim 2 ,5-a]pyrimidine claim 2 , or a pharmaceutically acceptable salt thereof.4. The method of claim 1 , wherein said disease is obesity.5. The method of claim 1 , wherein said disease selected from Alzhheimer's disease or Huntington's disease.6. The method of claim 1 , wherein said disease selected from psychotic disorder or schizophrenia.7. The method of claim 1 , wherein said disease selected from the group claim 1 , consisting of neurological disorder claim 1 , hypoxia-ischemia claim 1 , hypoglycemia claim 1 , convulsive state claim 1 , brain injury claim 1 , ...

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Номер записи: 11
28-03-2013 дата публикации

PYRIDO[3,4-B]INDOLES AND METHODS OF USE

Номер: US20130079352A1
Автор: CHAKRAVARTY Sarvajit, DUGAR Sundeep, HUNG David T., JAIN Rajendra Parasmal, PROTTER Andrew Asher
Принадлежит: MEDIVATION TECHNOLOGIES, INC.

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[3,4-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted C-Calkyl.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Q is phenyl or substituted phenyl.4. The compound according to claim 1 , wherein any one or more of (i)-(xi) apply claim 1 , provided that provisions (iv) and (v) are not combined claim 1 , provisions (ii) and (xi) are not combined and (iii) and (xi) are not combined:(i) q and m are both 0;{'sup': '11', '(ii) Ris H;'}{'sup': '12', 'sub': 1', '8, '(iii) Ris an unsubstituted C-Calkyl;'}{'sup': 3a', '3b, '(iv) one of Rand Ris methyl, ethyl or phenyl and the other is H;'}{'sup': 3a', '3b, '(v) Rand Rare both H;'}{'sup': '1', 'sub': 1', '8, '(vi) Ris an unsubstituted C-Calkyl;'}{'sup': 9', '4', '4, 'sub': 1', '8, '(vii) Xis CRwhere Ris unsubstituted C-Calkyl or halo;'}{'sup': 7', '8', '10', '4', '4, '(viii) X, Xand Xare each CRwhere Ris H;'}{'sup': 2a', '2b, '(ix) Rand Rare both H;'}{'sup': 10a', '10b, '(x) Rand Rare both H; and'}{'sup': 11', '12, '(xi) Rand Rare taken together to form a bond.'}6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein any one or more of (i)-(viii) apply claim 5 , provided that if any of provisions (ii) claim 5 , (iii) or (iv) applies claim 5 , only one of (ii) claim 5 , (iii) and (iv) applies:(i) q is 0;{'sup': 8c', '8d', '8e', '8f, '(ii) Rand Rare both H and Rand Rare independently H, hydroxyl or methyl;'}{'sup': 8c', '8e', '8d', '8f, '(iii) Ris taken together with Rto form a bond and ...

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Номер записи: 12
04-04-2013 дата публикации

ANTI-VIRAL TREATMENT AND ASSAY TO SCREENFOR ANTI-VIRAL AGENT

Номер: US20130085133A1
Автор: Ananthan Subramaniam, Chung Dong Hong, Jonsson Colleen B., Maddox Clinton Boykin, Maddry Joseph A., Pathak Ashish K., Rasmussen Lynn, Severson Bill, White Ellie Lucile
Принадлежит: Sourthern Research Institute Office of Commercialization and Intellectual Prop.

The present disclosure relates to novel compounds of formulas (1) through (19) and to a method for treating humans infected with a virus including various respiratory viruses such as members of the Paramyxoviridae family (respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), measles virus, and mumps virus) with a compound of formulas (1) through (19). The present disclosure also relates to a cytopathic effect (CPE)-based assay that will assess virus-induced CPE for screening of compounds for treating viral diseases or inhibiting a virus. 2. The method of wherein the virus is a respiratory virus.3. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 1 , human metapneumovirus claim 1 , human parainfluenza virus claim 1 , measles virus claim 1 , and mumps virus.4. The method of wherein the virus is respiratory syncytial virus.6. The method of wherein the virus is a respiratory virus.7. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 5 , human metapneumovirus claim 5 , human parainfluenza virus claim 5 , measles virus claim 5 , and mumps virus.8. The method of wherein the virus is respiratory syncytial virus.9. A method for screening for compounds for use as an anti-viral agent against a virus which comprises obtaining frozen cells infected with said virus claim 5 , thawing said infected cells and mixing said infected cells with uninfected cells of the same type as the infected cells claim 5 , contacting the mixture of said infected cells and uninfected cells with a compound to be screened and determining the viability of said cells.10. The method of wherein the virus is a respiratory virus.11. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 9 , human metapneumovirus claim 9 , human parainfluenza virus claim 9 , measles virus claim 9 , and mumps virus. ...

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Номер записи: 13
04-04-2013 дата публикации

QUINOXALINE COMPOUND

Номер: US20130085134A1
Автор: Azami Hidenori, KAIZAWA Hiroyuki, KAMIJO Kazunori, Kubota Hideki, Nomura Takaho, SEO Ryushi, SUGITA Mari, TSUCHIYA Kazuyuki, YAMAMOTO Hirofumi, YAMAMOTO Satoshi
Принадлежит: Astellas Pharma Inc.

Quinoxaline compounds of formula (I) have a PDE9-inhibiting action and are useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like. 116-. (canceled)18. The method of claim 17 , wherein Ris hydrogen or lower alkyl and Ris a group of the formula (II) claim 17 , or Ris a group of the formula (II) and Ris hydrogen; halogen; or lower alkyl claim 17 , —O-lower alkyl or cycloalkyl claim 17 , each of which may be substituted with one or more substituents selected from the group consisting of —OH claim 17 , —O-lower alkyl claim 17 , —NH claim 17 , —NH-lower alkyl claim 17 , —N(lower alkyl) claim 17 , and a monocyclic nitrogen-containing hetero ring which may further be substituted with lower alkyl.19. The method of claim 17 , wherein{'sup': '1', 'Ris a group of the formula (II),'}{'sup': '2', 'sub': 2', '2, 'Ris halogen; cycloalkyl; or lower alkyl or —O-lower alkyl, each of which may be substituted with a substituent selected from the group consisting of —OH, —O-lower alkyl, —NH, —NH-lower alkyl, —N(lower alkyl)and a monocyclic nitrogen-containing hetero ring which may further be substituted with lower alkyl; and'}{'sup': 4', '5', '6, 'R, Rand Rare hydrogen atoms.'}20. The method of claim 19 , wherein{'sup': '3', 'sub': 2', '2', '2, 'Ris lower alkyl which is substituted with cycloalkyl and which may further be substituted with 1 to 3 substituents selected from the group consisting of —OH, oxo and halogen; lower alkyl which may be substituted with a monocyclic sulfur-containing saturated hetero ring; or cycloalkyl or a monocyclic saturated hetero ring, each of which may be substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, —OH, oxo, —O-lower alkyl, —COOH, —CO—O-lower alkyl, —CO—O-lower alkenyl, lower alkynyl, —CO—O-lower alkylene-O-lower alkyl, —CO—O-lower alkylene-aryl, —CO—O-lower alkylene-O-aryl, —CO—NH, —CO—NH-lower alkyl, ...

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Номер записи: 14
04-04-2013 дата публикации

NOVEL ANTIFUNGAL 5,6-DIHYDRO-4-[(DIFLUOROETHYL)PHENYL]-4H-PYRROLO[1,2-a][1,4]BENZODIAZEPINE AND 4-(DIFLUOROETHYL)PHENYL-6H-PYRROLO[1,2-a][1,4]BENZODIAZEPINE DERIVATIVES

Номер: US20130085136A1
Автор: de Wit Kelly, Maes Louis Jules Roger Marie, Meerpoel Lieven
Принадлежит:

The present invention concerns novel compounds of Formula (I): 2. The compound according to claim 1 , wherein Ris chloro or fluoro.3. The compound according to claim 1 , wherein Ris chloro or fluoro; and wherein{'sup': '2', 'Ris chloro, fluoro or methyl.'}4. The compound according to claim 1 , wherein{'sup': '1', 'Ris chloro or fluoro;'}{'sup': '2', 'Ris hydrogen, chloro, fluoro or methyl;'}{'sup': 3', '4, 'Rand Rare taken together to form a bond;'}{'sup': 5', '6, 'Ris 1,1-difluoroethyl, and Ris hydrogen or fluoro;'}{'sup': 5', '6, 'or Ris hydrogen or fluoro, and Ris 1,1-difluoroethyl.'}5. The compound according to claim 1 , wherein{'sup': '1', 'Ris chloro or fluoro;'}{'sup': '2', 'Ris hydrogen;'}{'sup': 3', '4, 'Rand Rtaken together form a bond;'}{'sup': '5', 'Ris 1,1-difluoroethyl;'}{'sup': '6', 'Ris hydrogen.'}6. The compound according to claim 1 , wherein{'sup': '1', 'Ris in the 7-position and is chloro or fluoro; and'}{'sup': '2', 'Ris in any of the other positions and is hydrogen, chloro, fluoro or methyl.'}7. The compound according to claim 1 , wherein the compound is 7-chloro-4-[4-(1 claim 1 ,1-difluoroethyl)phenyl]-6H-pyrrolo[1 claim 1 ,2-a][1 claim 1 ,4]benzodiazepine.8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and claim 1 , as active ingredient claim 1 , a therapeutically effective amount of a compound as defined in any one of to .9. A compound as defined in any one of to for use as a medicament.10. A compound as defined in any one of to for use in the treatment or prevention of a fungal infection.11CandidaAspergillusCryptococcus neoformans; Sporothrix schenckii; Epidermophyton floccosum; MicrosporumTrichophytonFusariumRhizomucorMucor circinelloides; RhizopusMalassezia furfur; AcremoniumPaecilomyces; Scopulariopsis; ArthrographisScytalidium; ScedosporiumTrichodermaPenicilliumPenicillium marneffei;Blastoschizomyces.. The compound for use according to wherein the fungal infection is caused by one or more of the fungi ...

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Номер записи: 15
04-04-2013 дата публикации

SUBSTITUTED OCTAHYDROPYRROLO[1,2-a]PYRAZINE SULFONAMIDES AS CALCIUM CHANNEL BLOCKERS

Номер: US20130085141A1
Автор: LI Tao, Patel Sachin V., Perner Richard J., Randolph John T., Schrimpf Michael R., Woller Kevin R., Xia Zhiren, Zhang Qingwei
Принадлежит: AbbVie Inc.

The present application relates to: (a) compounds of Formula (I): 2. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sub': '2', 'Z′ and Z″ are each CH;'}{'sup': 1', '1', '1, 'Ris G-L-; and'}{'sup': '2', 'Ris hydrogen.'}3. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sub': '2', 'Z′ is CHand Z″ is C(O);'}{'sup': 1', '1', '1, 'Ris G-L-; and'}{'sup': '2', 'Ris hydrogen.'}4. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sub': '2', 'Z′ is C(O) and Z″ is CH;'}{'sup': 1', '1', '1, 'Ris G-L-; and'}{'sup': '2', 'Ris hydrogen.'}5. The compound of claim 1 , or a salt thereof claim 1 , wherein Lis —C(O)NR— claim 1 , —NRC(O)— claim 1 , —NR— claim 1 , or —O—.6. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sup': 1', '1', 'a, 'Gis —Ar-G;'}{'sup': '1', 'Aris pyridinyl or pyrazinyl; and'}{'sup': 'a', 'Gis cyclopropyl.'}7. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sup': 2', '2, 'Gis Ar; and'}{'sup': 2', '2, 'sub': 1', '4, 'Aris phenyl or pyridinyl; wherein Aris unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, cyano, C-C-alkyl, halomethyl, methoxy, and halomethoxy.'}8. The compound of claim 1 , or a salt thereof claim 1 , wherein:{'sup': 1', 'c', 'd', 'a', 'a', 'a, 'Lis —C(R)(R)—, —C(O)NR—, —NRC(O)—, —NR—, or —O—;'}{'sup': a', 'b, 'Rand R, at each occurrence, are each hydrogen;'}{'sup': c', 'd, 'Rand Rare each independently hydrogen or hydroxy;'}{'sup': 1', '1, 'sub': 1', '4', '2', '4', '1', '4', '1', '4, 'Aris, at each occurrence, independently selected from the group consisting of phenyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, and benzoxazolyl; wherein Aris unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, cyano, C-C-alkyl, C-C-alkenyl, C-C-haloalkyl, and C-C-haloalkoxy;'}{'sup': 'a', 'Gis cyclopropyl, cyclobutyl, or imidazolyl;'}{'sup': '2', 'sub': 2', '2', '2, ...

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Номер записи: 16
04-04-2013 дата публикации

SUBSTITUTED OCTAHYDROPYRROLO[1,2-a]PYRAZINES AS CALCIUM CHANNEL BLOCKERS

Номер: US20130085142A1
Автор: LI Tao, Patel Sachin V., Perner Richard J., Randolph John T., Schrimpf Michael R., Woller Kevin R., Xia Zhiren, Zhang Qingwei
Принадлежит: AbbVie Inc.

The present application relates to: (a) compounds of Formula (I): 2. The compound according to claim 1 , or a salt thereof claim 1 , wherein Z claim 1 , Z claim 1 , Zand Zare each CH.3. The compound according to claim 1 , or a salt thereof claim 1 , wherein:{'sup': 1', '1', '1, 'Ris G-L-;'}{'sup': '2', 'Ris hydrogen; and'}{'sup': 3', '2', '2, 'Ris -L-G.'}4. The compound according to claim 1 , or a salt thereof claim 1 , wherein:{'sup': 1', 'a', 'a, 'Lis —C(O)NR— or —NRC(O)—;'}{'sup': 1', '1', '1', '1', 's, 'sub': 1', '4', '2', '4', '2', '4', '1', '4, 'Gis Ar, wherein Aris aryl or heteroaryl, wherein Aris unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C-C-alkyl, C-C-alkenyl, C-C-alkynyl, halogen, cyano, —OR, and C-C-haloalkyl;'}{'sup': '2', 'Lis —C(O)O—; and'}{'sup': '2', 'sub': 1', '8', '1', '8, 'Gis C-C-alkyl or C-C-haloalkyl.'}5. The compound according to claim 1 , or a salt thereof claim 1 , wherein:{'sup': 1', 'a', 'a, 'Lis —C(O)NR— or —NRC(O)—;'}{'sup': 1', '1', '1', '1', 's, 'sub': 1', '4', '2', '4', '2', '4', '1', '4, 'Gis Ar, wherein Aris aryl or heteroaryl, wherein Aris unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C-C-alkyl, C-C-alkenyl, C-C-alkynyl, halogen, cyano, —OR, and C-C-haloalkyl;'}{'sup': '2', 'Lis —C(O)—; and'}{'sup': 2', '2', '2', '2', 'u, 'sub': 1', '4', '2', '4', '2', '4', '1', '4, 'Gis Ar, wherein Aris aryl or heteroaryl, wherein Aris unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C-C-alkyl, C-C-alkenyl, C-C-alkynyl, halogen, cyano, —OR, and C-C-haloalkyl.'}6. The compound according to or a salt thereof claim 1 , wherein:{'sup': 1', 'a', 'a, 'Lis —C(O)NR— or —NRC(O)—;'}{'sup': 1', '1', '1', '1', 's, 'sub': 1', '4', '2', '4', '2', '4', '1', '4, 'Gis Ar, wherein Aris aryl or heteroaryl, wherein Aris unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group ...

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Номер записи: 17
04-04-2013 дата публикации

NOVEL 2-PYRIDINECARBOXAMIDE DERIVATIVES

Номер: US20130085156A1
Автор: BAMBA MAKOTO, EIKI JUN-ICHI, MITSUYA MORIHIRO, Nishimura Teruyuki, SAKAI FUMIKO, SASAKI YASUHIRO, WATANABE HITOMI
Принадлежит: MSD K.K.

The present invention relates to a compound which has a glucokinase-activating effect and is useful as a therapeutic agent for diabetes mellitus, being represented by a formula (I): 138-. (canceled)40. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein D is S.41. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein both of Rand Rare hydrogen atoms.42. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein Xis selected from the group consisting of: a nitrogen atom claim 39 , sulfur atom claim 39 , oxygen atom claim 39 , —CH— claim 39 , —N—CH— claim 39 , —S—CH— claim 39 , —O—CH— claim 39 , —CH—N— claim 39 , —CH—O— claim 39 , and —CH—S—.43. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein the substituent on ring A is a hydrogen atom claim 39 , lower alkyl group claim 39 , lower alkoxy group claim 39 , hydroxy group claim 39 , or hydroxy lower alkyl group (the hydrogen atom of the hydroxy group of the hydroxy lower alkyl group may further be substituted by a lower alkyl group).44. The compound of claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein the substituent on ring B is a hydrogen atom claim 39 , lower alkyl group claim 39 , halogen atom claim 39 , hydroxyalkyl group claim 39 , aminoalkyl group claim 39 , or alkanoyl group.45. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein Rrepresents a pyridyl group.46. The compound according to claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein the substituent in Ris hydrogen atom claim 39 , hydroxyalkyl group claim 39 , lower alkyl group claim 39 , lower alkoxy group claim 39 , carbamoyl group claim 39 , alkylcarbamoyl group claim 39 , dialkylcarbamoyl group claim 39 , cyano group claim 39 , trifluoromethyl group claim 39 , ...

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Номер записи: 18
11-04-2013 дата публикации

N-CONTAINING HETEROCYCLIC COMPOUNDS

Номер: US20130090336A1
Автор: Bourke David Gerard, Burns Christopher John, Cuzzupe Anthony Nicholas, Feutrill John Thomas, KLING Marcel Robert, Nero Tracy Leah
Принадлежит: YM Biosciences Australia Pty Ltd

The present invention relates to N-containing heterocyclic compounds that are inhibitors of protein kinases including JAK kinases. In particular, the compounds are selective for JAK1, JAK2, JAK3 or TYK2 kinases and combinations thereof such as JAK1 and JAK2. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases. 4. The compound according to claim 1 , wherein A is absent claim 1 , substituted or unsubstituted Calkylene or substituted or unsubstituted divalent Calkoxy and B is absent or S.5. The compound according to claim 1 , wherein R is independently selected from H claim 1 , halogen claim 1 , COR claim 1 , CONRR claim 1 , Ccycloalkyl claim 1 , 5 or 6 membered aryl and 5 to 8 membered heterocyclyls having up to 3 heteroatoms selected from N claim 1 , O claim 1 , S and SO claim 1 , each of which may be substituted with up to 3 substituents independently selected from substituted or unsubstituted Calkyl claim 1 , substituted or unsubstituted 5 to 8 membered heterocyclyls having up to 3 heteroatoms selected from N claim 1 , O claim 1 , S and SO claim 1 , ROH claim 1 , RNHCOR claim 1 , OCF claim 1 , substituted or unsubstituted Calkoxy claim 1 , OH claim 1 , NRR claim 1 , SONRR claim 1 , NRSOR claim 1 , NRCOR claim 1 , CONRR claim 1 , NRCONRR claim 1 , COR claim 1 , CORand/or SORwherein Rand Rare as defined in .6. The compound according to claim 1 , wherein R is independently selected from phenyl unsubstituted or substituted with at least one of NRR claim 1 , NRCOR claim 1 , substituted or unsubstituted Calkoxy claim 1 , substituted or unsubstituted 5 to 8 membered heterocyclyls having up to 3 heteroatoms selected from N claim 1 , O claim 1 , S and SO claim 1 , SONRR claim 1 , NRCONRR claim 1 , NRSOR claim 1 , ROH claim 1 , RNHCOR ...

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Номер записи: 19
11-04-2013 дата публикации

3,4-DIHYDROPYRROLO[1,2-A]PYRAZINE-2,8(1H)-DICARBOXAMIDE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

Номер: US20130090340A1
Автор: COTE-DES-COMBES Sylvain, FROISSANT Jacques, GIBERT Jean-Francois, MARGUET Frank, PACAUD Christophe, PUECH Frederic, RAVET Antoine
Принадлежит: SANOFI

Compounds corresponding to the general formula (I) 2. The compound of formula (I) according to claim 1 , wherein{'sub': '2', 'Rrepresents{'sub': 1-10', '3-7', '1-6', '1-6', '1-10', '1-10', '1-6', '3-7', '1-6', '1-10, 'a group C-alkyl, C-cycloalkyl-C-alkyl, C-alkoxy-C-alkyl, hydroxy-C-alkyl, hydroxy-C-alkyl-C-cycloalkyl-C-alkyl, or C-fluoroalkyl;'}{'sub': 3-10', '3-10', '3-10, 'a group C-cycloalkyl, C-fluorocycloalkyl, or hydroxy-C-cycloalkyl;'}{'sub': 3-7', '1-6', '3-7', '1-10', '1-10, 'a group C-cycloalkyl which may be substituted with one or two groups independently chosen from C-alkyl, C-cycloalkyl, hydroxyl, C-fluoroalkyl and C-alkyl-oxyimino;'}{'sub': '1-6', 'a heterocyclic group comprising from 3 to 8 carbon atoms and at least one heteroatom chosen from oxygen or a sulfur atom in dioxide form, this heterocyclic group possibly being substituted with one or more groups C-alkyl; or'}{'sub': 1-10', '1-6, 'a group C-alkyl substituted with a heterocyclic group comprising from 3 to 8 carbon atoms and at least one oxygen heteroatom, this heterocyclic group possibly being substituted with one or more groups C-alkyl;'}{'sub': 7', '7, 'claim-text': a fluorine or chlorine atom,', 'or a group chosen from', {'sub': 1-6', '3-7, 'C-cycloalkyl, C-cycloalkyl,'}], 'Rrepresents a phenyl group optionally substituted with one or more substituents X, which may be identical or different, chosen independently from{'sub': 1-6', '3-7', '1-6, 'claim-text': [{'sub': '1-6', 'C-alkylthio,'}, 'aryl,', {'sub': '1-6', 'aryloxy, aryl-C-alkoxy,'}, {'sub': 1', '6, 'C-fluoroalkyl,'}, {'sub': 1', '6, 'C-fluoroalkoxy,'}, {'sub': '1-6', 'cyano, cyano-C-alkoxy,'}, {'sub': a', 'b', 'c', '2', 'd', 'c', '2', 'a', 'b', 'a', 'b', 'c', 'd, 'NRR, NRSOR, NRSONRR, CONRR, CON (OR) R, and'}, {'sub': '1-6', 'heteroaryl chosen from an oxadiazolyl and pyrazolyl group, optionally substituted with a group C-alkyl, the aryl group being optionally substituted with a fluorine atom;'}], 'C-alkoxy, C-cycloalkyl-C-alkoxy ...

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Номер записи: 20
18-04-2013 дата публикации

COMPOUNDS FOR ELECTRONIC DEVICES

Номер: US20130092879A1
Автор: Brocke Constanze, Fortte Rocco, Parham Amir Hossain, Pflumm Christof
Принадлежит: Merck Patent GmBH

The present invention relates to compounds of the formula (I), to the use of compounds of the formula (I) in electronic devices, and to electronic devices comprising one or more compounds of the formula (I). The invention furthermore relates to preparation processes for compounds of the formula (I) and to formulations comprising one or more compounds of the formula (I). 114-. (canceled)16. The compound according to claim 15 , wherein X claim 15 , Xand Xare on each occurrence claim 15 , identically or differently claim 15 , from C(R) claim 15 , C═O claim 15 , NR claim 15 , O or S.17. The compound according to claim 15 , wherein one of the two groups Xand Xis equal to CRand the other is equal to N.18. The compound according to claim 15 , wherein all three groups X claim 15 , Xand Xdo not simultaneously represent O.19. The compound according to claim 15 , wherein all three groups X claim 15 , Xand Xdo not simultaneously represent S.21. The compound according to claim 15 , wherein not more than three groups Z per aromatic ring are equal to N and the remaining groups Z are equal to CR.23. An oligomer claim 15 , polymer or dendrimer comprising one or more compounds according to claim 15 , where the bond(s) to the polymer claim 15 , oligomer or dendrimer is optionally localised at any positions in formula (I) substituted by a radical Ror R.24. A formulation comprising at least one compound according to and at least one solvent.25. A formulation comprising at least one polymer claim 23 , oligomer or dendrimer according to and at least one solvent.26. An electronic device which comprises the compound according to .27. An electronic device which comprises the polymer claim 23 , oligomer or dendrimer according to .28. The electronic device according to claim 26 , wherein the device is an organic electroluminescent device (OLED).29. An emitting layer of an electronic device which comprises the compound according to as matrix material in combination with one or more further ...

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Номер записи: 21
18-04-2013 дата публикации

IMIDAZOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Номер: US20130096104A1
Автор: Lai Yingjie, Liang Jun, Magnuson Steven R., Robarge Kirk D., Tsui Vickie H., Zhang Birong, Zhou Aihe
Принадлежит: Genentech, Inc.

The invention provides compounds of Formulas Ia-Ib, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, X, R, R, R, Rand Rare defined herein, a pharmaceutical composition that includes a compound of Formulas Ia-Ib and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of using the compound or composition in therapy, as an inhibitor of TYK2 kinase and conditions related, such as inflammatory illnesses, inflammatory bowel disease or psoriasis. 2. The compound of claim 1 , wherein A is CRand X is CR.3. The compound of claim 1 , wherein A is CRand X is N.43. The compound of any one of - claims 1 , wherein Ris independently hydrogen claims 1 , halogen claims 1 , C-Calkyl claims 1 , —CF claims 1 , —OR claims 1 , —SR claims 1 , —OCF claims 1 , —NOor —NRR claims 1 , wherein both Rcannot be hydrogen at the same time claims 1 , and wherein said alkyl is optionally substituted by halogen claims 1 , ORor —NRR.53. The compound of any one of - claims 1 , wherein one Ris halogen and the other Ris hydrogen claims 1 , halogen claims 1 , C-Calkyl claims 1 , C-Ccycloalkyl claims 1 , —CF claims 1 , —OH claims 1 , —O(C-Calkyl) claims 1 , —SH claims 1 , —S(C-Calkyl) claims 1 , —OCF claims 1 , —CN claims 1 , —NO claims 1 , —NHSOCH claims 1 , —NHC(O)Ror —NRR claims 1 , wherein said alkyl and cycloalkyl are optionally substituted by halogen claims 1 , OR claims 1 , —NRRor phenyl.65. The compound of any one of - claims 1 , wherein Ris independently hydrogen claims 1 , halogen or C-Calkyl optionally substituted by R. In certain embodiments claims 1 , Ris independently F claims 1 , Cl claims 1 , Br claims 1 , —CHOH claims 1 , —CHNHor —CHmorpholinyl.76. The compound of any one of - claims 1 , wherein A is CRand Ris hydrogen claims 1 , C-Calkyl claims 1 , C-Calkenyl claims 1 , C-Calkynyl claims 1 , halogen claims 1 , —(C-Calkyl)CN claims 1 , —(C-Calkyl)OR claims 1 , —(C-Calkyl)SR claims 1 , —(C-Calkyl)NRR claims 1 , —(C-Calkyl)C(O)NRR claims 1 , —(C-Calkyl ...

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Номер записи: 22
18-04-2013 дата публикации

CARBOLINE CARBOXAMIDE COMPOUNDS USEFUL AS KINASE INHIBITORS

Номер: US20130096118A1
Автор: DeLucca George V., Douglas Batt G., Lin James, Liu Chunjian, Liu Qingjie
Принадлежит:

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, formula (I) are useful as kinase modulators, including Btk modulation. 115-. (canceled)20. The compound according to claim 16 , wherein{'sup': 1', '2', '2', '2', '2', '2', '2', '11', '2', '2', '2', '2', '11', '2', '11', '11', '2', '11', '2', '11', '2', '11', '2, 'sub': 2', 'r', '2', '2, 'Dand Dare independently R, —(CH)R, —OR, —C(═O)R, —C(═O)OR, —C(═O)NRR, —S(O)R, —S(O)R, —SR, —NRC(O)R, —NRC(O)NRR, —NRC(═O)OR, —NRS(═O)R, or —NRR;'}{'sup': 2', '2a', '2a', '2a', '2a', '2a', '2a, 'sub': 1-6', '2-6', '3-10', '6-10, 'Ris hydrogen, Calkyl substituted with 0-3 R, Calkenyl substituted with 0-3 R, Ccycloalkyl substituted with 0-4 R, —Caryl substituted with 0-4 R, a 5-10 membered heterocyclyl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R, or a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R;'}{'sup': 2a', 'b', 'b', 'b', 'b', 'b', '11', '11', '11', '11', 'b', 'c', 'b', 'c', 'b', '11', '11', '11', '11', 'b', 'c', 'c', 'c', 'a', 'a', 'a, 'sub': 3', '3', '2', '2', 'p', 'p', '2', '1-6', '2', 'r', '2', 'r', 'p, 'Ris hydrogen, ═O, F, Cl, Br, OCF, CF, CHF, CN, NO, OR, SR, —C(O)R, —C(O)OR, —OC(O)R, —NRR, —C(O)NRR, —NRC(O)R, —NRC(O)OR, —NRC(O)NRR, —S(O)NRR, —NRS(O)R, —S(O)R, —S(O)R, Calkyl substituted with 0-2 R, —(CH)-3-14 membered carbocycle substituted with 0-1 R, wherein the carbocycle is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or —(CH)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)substituted with 0-2 R; and'}r is 0, 1, or 2.26. The compound according to claim 25 , wherein{'sup': a', 'b', 'b', 'b', 'b', 'b', '11', '11', '11', '11', 'b', 'c', 'b', 'c', 'b', '11', '11', '11', '11', 'b', 'c', 'c', 'c, 'sub': 3', '3', '2', '2', 'p', 'p', '2', '1-6', '1-6', '2', 'r', '2', 'r', 'p, 'Ris hydrogen, F, Cl, Br, OCF, CF, CHF ...

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Номер записи: 23
18-04-2013 дата публикации

CGRP Receptor Antagonists

Номер: US20130096130A1
Автор: Chen Ling, Dubowchik Gene M., Luo Guanglin, Macor John E.
Принадлежит:

The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD). 6. A compound of where Ris N-piperidinyl and is 4-substituted.8. A compound of where Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydroxy claim 1 , azido claim 1 , or amino claim 1 , and Ris hydrogen; or where Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen or hydroxy claim 1 , and Rand Rtaken together is oxo; or where Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydroxy claim 1 , Ris hydrogen or hydroxy claim 1 , and Ris hydrogen; or where Ris hydroxy claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , Ris hydrogen claim 1 , and Ris hydrogen.9. A compound of where Aris phenyl substituted with 2 halo substituents.10. A compound of where Aris 2 claim 9 ,3-difluorophenyl.11. A compound of where X is O.12. A compound of selected from the group consisting of(5R,8S,9S)-9-(tert-butoxycarbonylamino)-8-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate;(5R,8S,9S)-9-amino-8-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate;N-((5R,8S,9S)-9-amino-8-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-yl)-4-(2-oxo-2, ...

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Номер записи: 24
18-04-2013 дата публикации

Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof

Номер: US20130096146A1
Автор: Gangjee Aleem
Принадлежит:

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells. 2. The compound of comprising pharmaceutically acceptable salts claim 1 , prodrugs claim 1 , solvates claim 1 , or hydrates thereof.3. The compound of comprising wherein when the C ring is saturated or partially saturated claim 1 , the substituted Rcreates chirality when X is a C and Rand Rare different.4. The compound of comprising stereoisomers thereof.5. The compound of comprising a racemic and/or a diastereoisomeric mixture thereof.7. The compound of comprising pharmaceutically acceptable salts claim 6 , prodrugs claim 6 , solvates claim 6 , or hydrates thereof.8. The compound of comprising wherein when the C ring is saturated or partially saturated claim 6 , the substituted Rcreates chirality when X is a C and Rand Rare different.9. The compound of comprising stereoisomers thereof.10. The compound of comprising a racemic and/or a diastereoisomeric mixture thereof.12. The method of including administering to the patient a therapeutically effective amount of a pharmaceutical salt claim 11 , prodrug claim 11 , solvate claim 11 , or hydrate of said compound of Formula II. This application is a divisional utility patent application claiming priority to pending U.S. Utility patent application Ser. No. 13/151,530, filed on Jun. 2, 2011, which is a divisional application of and claims the benefit of priority to U.S. Utility patent application Ser. No. 12/170,633, filed on Jul. 10, 2008, now U.S. Pat. No. 7,982,035, granted on Jul. 19, 2011, which is a continuation-in-part application of and claims the benefit of priority to U.S. ...

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Номер записи: 25
18-04-2013 дата публикации

TRIAZOLOPYRIDINE COMPOUND, AND ACTION THEREOF AS PROLYL HYDROXYLASE INHIBITOR OR ERYTHROPOIETIN PRODUCTION-INDUCING AGENT

Номер: US20130096155A1
Автор: Abe Hiroyuki, HOTTA Takahiro, ITO Takashi, Matsui Takuya, Mitani Ikuo, MOTODA Dai, OGOSHI Yosuke, TERASHITA Masakazu, UEYAMA Kazuhito, YOKOTA Masahiro
Принадлежит: JAPAN TOBACCO INC.

The present invention provides a triazolopyridine compound having a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability. The present invention relates to a compound represented by the following formula [I]: 2. (canceled)6. The compound according to claim 1 , wherein both Rand Rare hydrogen atoms claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof7. The compound according to claim 1 , wherein Ris a hydrogen atom claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof.8. The compound according to claim 1 , wherein Ris a hydrogen atom claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof.9. The compound according to claim 1 , wherein{'sup': '2', 'Ris'}{'sub': '1-10', '(1) a Calkyl group,'}{'sub': '6-14', '(2) a Caryl group optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B,'}{'sub': 6-14', '1-6', '6-14, '(3) a Caryl-Calkyl group (wherein Caryl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B), or'}{'sub': 3-8', '1-6', '3-8, '(4) a Ccycloalkyl-Calkyl group (wherein Ccycloalkyl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B), or a pharmaceutically acceptable salt thereof, or a solvate thereof.'}1013.-. (canceled)1525.-. (canceled)26. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof claim 1 , and a pharmaceutically acceptable carrier.2734.-. (canceled)35. A method of inhibiting prolyl hydroxylase claim 1 , comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to a mammal.36. A method of inducing erythropoietin production claim 1 , comprising ...

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Номер записи: 26
18-04-2013 дата публикации

PYRROLOPYRAZINES AND PYRAZOLOPYRAZINES USEFUL AS INHIBITORS OF PROTEIN KINASES

Номер: US20130096302A1
Автор: Binch Hayley, Fraysse Damien, Miller Andrew, Robinson Daniel
Принадлежит:

The present invention relates to compounds useful as inhibitors of Aurora protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. 2. The compound according to wherein X is CH.3. The compound according to wherein X is N.4. The compound according to or claim 1 , wherein Ris a 5-6 membered aryl or heteroaryl.5. The compound according to claim 4 , wherein Ris a 5-6 membered heteroaryl.7. The compound according to wherein one claim 6 , two claim 6 , or three G groups are N.8. The compound according to wherein at least Gis nitrogen.98. The compound according any one of - wherein any two G groups selected from G claims 6 , G claims 6 , G claims 6 , G claims 6 , and Gare N.10. The compound according wherein only one G group is N.11. The compound according to claim 4 , wherein Ris phenyl optionally substituted with up to 5 J.1211. The compound according to any one of - claims 1 , wherein J is —U—(R)wherein{'sup': 6', '5', '4', '5, 'sub': 1-12', '3-10', '7-12', '6-10', '2, 'each Ris independently H or optionally substituted Caliphatic, Ccycloaliphatic, Cbenzofused cycloaliphatic, Caryl, 5-14 membered heterocyclyl, 5-14 membered heteroaryl, OR, N(R), or SR;'}{'sub': '1-6', 'U is a bond or Caliphatic wherein up to two methylene units are optionally replaced by Y in a chemically stable arrangement;'}{'sup': 5', '5', '5', '5', '5', '5', '5, 'sub': '2', 'Y is a group selected from —O—, —NR—, —S—, —NRC(O)—, —N(SO)—, —NRC(O)NR—, —C(O)NR—, —C(O)—, —OC(O)NR—, —NRC(O)O—, —C(O)O—, or —OC(O)—;'}n is 1 or 2.13. The compound according to claim 12 , wherein Y is —O— claim 12 , —NR— claim 12 , or —S—.14. The compound according to claim 12 , wherein Y—NR(C═O)— or —(C═O)NR—;15. The compound according to claim 12 , wherein Y is —NR—.1615. The compound according ...

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Номер записи: 27
18-04-2013 дата публикации

DEUTERATED HIV ATTACHMENT INHIBITORS

Номер: US20130096305A1
Автор: Meanwell Nicholas A., WANG TAO, Zhang Zhongxing
Принадлежит:

Deuterated piperazine and piperidine HIV attachment inhibitor compounds are set forth. The present invention provides compounds of Formula I, the pharmaceutically acceptable salts and/or solvates (e.g., hydrates) thereof, their pharmaceutical formulations, and their use in patients suffering from or susceptible to a virus such as HIV. The compounds of Formula I, their pharmaceutically acceptable salts and/or solvates are effective antiviral agents, particularly as inhibitors of HIV. They are useful for the treatment of HIV and AIDS. This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. In particular, the invention herein is directed to deuterated HIV attachment inhibitors that possess unique antiviral activity. More particularly, the present invention relates to deuterated piperazine and piperidine compounds useful for the treatment of HIV and AIDS.HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with an estimated 45 million people infected worldwide at the end of 2007. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2005, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the treatment of HIV include nucleoside reverse transcriptase (RT) inhibitors or approved single pill combinations: zidovudine (or AZT or RETROVIR®), didanosine (or VIDEX®), stavudine (or ZERIT®), lamivudine (or 3TC or EPIVIR®), zalcitabine (or DDC or HIVID®), abacavir succinate (or ZIAGEN®), tenofovir disoproxil fumarate salt (or VIREAD®), emtricitabine (or FTC-EMTRIVA®), COMBIVIR® (contains −3TC plus AZT), TRIZIVIR® (contains abacavir, lamivudine, and zidovudine), Epzicom (contains abacavir and lamivudine), TRUVADA® (contains VIREAD® and EMTRIVA®); non-nucleoside reverse transcriptase inhibitors: nevirapine (or VIRAMUNE®), delavirdine (or RESCRIPTOR®) and efavirenz (or ...

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Номер записи: 28
25-04-2013 дата публикации

Light-emitting device and photovoltaic cell, and method for manufacturing the same

Номер: US20130099224A1
Автор: Hideyuki Higashimura, Kenta Tanaka, Masanobu Tanaka, Takayuki Iljima
Принадлежит: Sumitomo Chemical Co Ltd

Provided are a light-emitting device and a photovoltaic cell having excellent characteristics. A light-emitting device ( 10 ) includes a cathode ( 34 ), an anode ( 32 ), a light-emitting layer ( 50 ) interposed between the cathode ( 34 ) and the anode ( 32 ), and an electron injection layer ( 44 ) provided between the cathode ( 34 ) and the light-emitting layer ( 50 ) and connected to the cathode ( 34 ), in which at least one of the anode ( 32 ) and the cathode ( 34 ) contains a conductive material having an aspect ratio of 1.5 or more, and the electron injection layer ( 44 ) contains an organic compound having at least one of an ionic group and a polar group.

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Номер записи: 29
25-04-2013 дата публикации

METHODS OF USING (+)-1,4-DIHYDRO-7-[(3S,4S)-3-METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID FOR TREATMENT OF ANTECEDENT HEMATOLOGIC DISORDERS

Номер: US20130102559A1
Автор: Michelson Glenn
Принадлежит:

Methods of treating, preventing or managing antecedent hematologic disorders, such as myelodysplastic syndrome, including chronic myelomonocytic leukemia are disclosed. The methods encompass the administration of SNS-595. Also provided are methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. In certain embodiments, the method of treatment comprise administering SNS-595 in combination with cytarabine. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods are also disclosed. 1. A method of treating an antecedent hematological disorder comprising administering to a mammal in need thereof a therapeutically effective amount of an enantiomerically pure (+)-1 ,4-dihydro-7-[(3S ,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1 ,8-naphthyridine-3-carboxylic acid.2. The method of claim 1 , wherein the antecedent hematological disorder is a myelodysplastic syndrome.3. The method of claim 1 , wherein the myelodysplastic syndrome is characterized by ineffective blood cell production claim 1 , progressive cytopenia claim 1 , risk of progression to acute leukemia or cellular marrow with impaired morphology.4. The method of claim 2 , wherein the myelodysplastic syndrome is selected from group consisting of refractory anemia claim 2 , refractory anemia with ringed sideroblasts claim 2 , refractory anemia with excess blasts claim 2 , refractory anemia with excess blasts in transformation claim 2 , and chronic myelomonocytic leukemia.5. The method of claim 2 , wherein the myelodysplastic syndrome is chronic myelomonocytic leukemia.6. The method of claim 5 , wherein the chronic myelomonocytic leukemia is relapsed claim 5 , refractory claim 5 , or resistant to conventional therapy.7. The method of claim 1 , further comprising administering a therapeutically effective amount of a second active agent.8. The method of claim 7 , wherein the second active ...

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Номер записи: 30
25-04-2013 дата публикации

SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS

Номер: US20130102586A1
Автор: Appalaneni Rajendra P., Krishna Reddy Y. Venkata, Vankayalapati Hariprasad
Принадлежит: ARRIEN PHARMACEUTICALS LLC

Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds. 4. The invention of wherein R claim 1 , Rand Rat each occurrence is independently —H claim 1 , optionally substituted Calkyl claim 1 , optionally substituted cycloalkyl claim 1 , optionally substituted heterocycloalkyl claim 1 , optionally substituted aryl or optionally substituted heteroaryl.5. The invention of wherein R claim 1 , Rand Rare each independently —NHCOCalkyl claim 1 , —NHCOcycloalkyl claim 1 , —NHCOheterocycloalkyl claim 1 , —CONHCalkyl claim 1 , —CONHcycloalkyl claim 1 , or —CONHheterocycloalkyl.6. The invention of wherein R claim 1 , Rand Rare each independently directly substituted by —H claim 1 , —F claim 1 , —Cl claim 1 , —OCF claim 1 , CF claim 1 , —CH claim 1 , —OCHFor —OCH claim 1 , wherein at least one of RRand Ris not hydrogen.10. The invention of wherein ZRis directly substituted by —H claim 9 , —F claim 9 , —Cl claim 9 , —OCF claim 9 , CF claim 9 , —CH claim 9 , —OCHFor —OCH claim 9 , wherein at least one of Ris not hydrogen;15. A compound according to which is a protein kinase inhibitor.16. A compound according to wherein the compound is an inhibitor of a protein kinase selected from the group consisting of ...

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Номер записи: 31
25-04-2013 дата публикации

PYRAZOLO [4,3-C] CINNOLIN-3-ONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

Номер: US20130102599A1
Автор: Beshore Douglas C., Kuduk Scott D.
Принадлежит:

The present invention is directed to pyrazolo[4,3-c]cinnolin-3-one compounds of formula (I) 123-. (canceled)25. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris phenyl which is optionally substituted by one or more(a) halogen,(b) hydroxy,{'sub': '1-6', '(c) —O—Calkyl,'}{'sub': '1-6', '(d) —Calkyl, and'}(e) cyano.26. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris heteroaryl claim 24 , which is optionally substituted by one or more(a) halogen (for example fluoro, chloro or bromo),(b) hydroxy,{'sub': '1-6', '(c) —O—Calkyl,'}{'sub': '1-6', '(d) —Calkyl, and'}(e) cyano.27. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris heterocyclic claim 24 , which is optionally substituted by one or more(a) hydroxy, or{'sub': '1-6', '(b) —Calkyl.'}28. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris cycloalkyl claim 24 , alkyl or alkenyl claim 24 , each of which are optionally substituted by one or more(a) hydroxy, or(b) halogen.29. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris phenyl claim 24 , which is optionally substituted with one or more(a) halogen,(b) hydroxy,{'sub': '1-6', '(c) —O—Calkyl,'}{'sub': '1-6', '(d) —Calkyl,'}(e) —CN,{'sup': A', 'B, '(f) —NRR,'}{'sub': '1-6', '(g) —NH(C═O)—Calkyl,'}{'sup': A', 'B, 'claim-text': (i) hydrogen, or', {'sub': '1-6', '(ii) —Calkyl,'}, {'sup': A', 'B, 'or Rand Rare linked together with the nitrogen to which they are both attached to form a 2-6 membered carbocyclic ring, wherein one or two of the ring carbon atoms is replaced by a nitrogen, oxygen or sulfur,'}], 'wherein Rand Rare selected from the group consisting of'}30. A compound of claim 24 , or a pharmaceutically acceptable salt thereof claim 24 , wherein Ris heteroaryl claim 24 , which is optionally substituted with one or more(a) halogen,(b) hydroxy,{'sub': ...

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Номер записи: 32
25-04-2013 дата публикации

2,4-DIARYL - SUBSTITUTED [1,8] NAPHTHYRIDINES AS KINASE INHIBITORS FOR USE AGAINST CANCER

Номер: US20130102603A1
Автор: Amendt Christiane, Dorsch Dieter, Hoelzemann Guenter, Jonczyk Alfred, Zenke Frank
Принадлежит: Merck Patent Gesellschaft Mit Beschrankter Haftung

The present invention relates to novel [1,8]naphthyridine derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases plays a role, particularly to inhibitors of TGF-beta receptor kinases, and to the use of such compounds for the treatment of kinase-induced diseases, in particular for the treatment of tumors. 2. Compound according to claim 1 , with the further proviso that Wdenotes N and/or Z excludes N═C claim 1 , i.e. Z denotes C═C claim 1 , N(R)CO claim 1 , NR claim 1 , C═N claim 1 , O claim 1 , CON(R) claim 1 , S claim 1 , CH or N═N claim 1 ,and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.3. Compound according to claim 1 , wherein Z is selected from the group consisting of:(a) C═C, or{'sup': '4', '(b) N(R)CO, or'}{'sup': '4', '(c) NR, or'}(d) C═N, or(e) O, or{'sup': '4', '(f) CON(R),'}and preferably is C═C,and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.6. Compound according to claim 1 , wherein{'sup': '2', 'sub': n', '2', 'n', 'n', 'n', 'n', 'n', 'n', '3, 'Ris absent or denotes H, A, Hal, —(CYY)—OY, NO, —(CYY)—NYY, —(CYY)-Het, —O—(CYY)-Het, —O—(CYY)—OY, —O—(CYY)—NYY, NY—(CYY)—NYY, NY—COY or a monocyclic heteroaryl having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 C atoms and 1, 2, 3, 4 or 5 N, O and/or S atoms, where the monocyclic heteroaryl can be independently substituted by at least one substituent selected from the group consisting of Y, Hal, CN, CFor OY, and the physiologically acceptable salts, solvates, stereoisomers and tautomers thereof, including mixtures thereof in all ratios.'}10. A method for inhibiting ATP consuming proteins claim 1 , preferably TGF-beta receptor kinase claim 1 , RON claim 1 , TAK1 claim 1 , PKD1 claim 1 , MINK1 claim 1 , SAPK2-alpha claim 1 , SAPK2-beta and/or ...

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Номер записи: 33
25-04-2013 дата публикации

IP RECEPTOR AGONIST HETEROCYCLIC COMPOUNDS

Номер: US20130102611A1
Автор: Charlton Steven John, Leblanc Catherine, McKeown Stephen Carl
Принадлежит: NOVARTIS AG

The present invention provides heterocyclic derivatives which activate the IP receptor. Activating the IP receptor signaling pathway is useful to treat many forms of PAH, pulmonary fibrosis and exert beneficial effects in fibrotic conditions of various organs in animal models and in patients. Pharmaceutical compositions comprising such derivatives are also encompassed. Examples of compounds of the invention include the compounds according to Formula Ia, or a pharmaceutically acceptable salt thereof, and the compounds of the examples. 2. The compound according to claim 1 , wherein{'sup': '1', 'Ris X—Y;'}{'sup': '2', 'sub': 1', '8, 'Ris H, or C-Calkyl optionally substituted by one or more halogen atoms;'}{'sup': '2a', 'Ris hydrogen;'}{'sub': 1', '6', '1', '4, 'X is C-Calkylene optionally substituted by hydroxy, halogens or C-Calkyl;'}{'sup': x', 'x', 'x, 'sub': q', '1', '4, 'Y is —C(O)OH, —C(O)ORor —CONH—S(O)—R, wherein Ris —C-Calkyl;'}q is 2;{'sup': '3', 'sub': 1', '4', '3', '7', '1', '4, 'Ris H, C-Calkoxy, OH, CN, halogen, C-Ccycloalkyl or C-Calkyl optionally substituted by one or more halogen atoms;'}{'sup': '4', 'sub': 1', '4', '3', '7', '1', '4, 'Ris H, C-Calkoxy, OH, CN, halogen, C-Ccycloalkyl or C-Calkyl optionally substituted by one or more halogen atoms.'}3. The compound according to claim 1 , wherein{'sup': 1', '7, 'sub': 2', 'm', '2', 'm', '2', 'n, 'Ris X—Y, wherein X—Y is —(CH)—C(O)OR″, or —(CH)—R—(CH)—C(O)OR″;'}{'sup': '2', 'sub': 1', '4, 'Ris H, C-Calkyl optionally substituted by one or more halogen atoms;'}{'sup': '2a', 'Ris hydrogen;'}{'sup': '3', 'sub': 1', '4', '3', '7', '1', '4, 'Ris H, C-Calkoxy, OH, CN, halogen, C-Ccycloalkyl or C-Calkyl optionally substituted by one or more halogen atoms;'}{'sup': '4', 'sub': 1', '4', '3', '7', '1', '4, 'Ris H, C-Calkoxy, OH, CN, halogen, C-Ccycloalkyl or C-Calkyl optionally substituted by one or more halogen atoms;'}{'sub': 1', '4, 'R″ is H or C-Calkyl optionally substituted by one or more halogen atoms;'}m is 1 ...

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Номер записи: 34
25-04-2013 дата публикации

TREATMENT OF CANCER WITH TOR KINASE INHIBITORS

Номер: US20130102613A1
Автор: Chopra Rajesh, Hege Kristen Mae, Lopez-Girona Antonia, Narla Rama K., Raymon Heather, Xu Shuichan
Принадлежит: SIGNAL PHARMACEUTICALS, LLC

Provided herein are methods for treating or preventing a solid tumor, non-Hodgkin lymphoma or multiple myeloma in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a solid tumor, non-Hodgkin lymphoma or multiple myeloma. 1. A method for treating a solid tumor , non-Hodgkin lymphoma or multiple myeloma , comprising administering an effective amount of a TOR kinase inhibitor of formula (I) , (Ia) , (Ib) , (Ic) , (Id) , (Ie) , (If) , (Ig) , (II) , (IIa) , (IIb) , (IIc) , (IId) , (III) , or (IV) to a patient having a solid tumor , non-Hodgkin lymphoma or multiple myeloma.2. The method of claim 1 , wherein the solid tumor is an advanced solid tumor.3. The method of claim 1 , wherein the solid tumor is a neuroendocrine tumor.4. The method of claim 3 , wherein the neuroendocrine tumor is of gut origin claim 3 , of non-pancreatic origin claim 3 , or of unknown primary origin.5. The method of claim 3 , wherein the neuroendocrine tumor is a symptomatic endocrine producing tumor or a nonfunctional tumor.6. The method of claim 3 , wherein the neuroendocrine tumor is locally unresectable claim 3 , metastatic moderate claim 3 , well differentiated claim 3 , low (grade 1) or intermediate (grade 2).7. The method of claim 1 , wherein the solid tumor is non-small cell lung cancer claim 1 , glioblastoma multiforme claim 1 , hepatocellular carcinoma claim 1 , breast cancer claim 1 , colorectal cancer claim 1 , salivary cancer claim 1 , pancreatic cancer claim 1 , adenocystic cancer or adrenal cancer.8. The method of claim 7 , wherein the breast cancer is ER+/Her2− claim 7 , ER+/Her2+ claim 7 , ER−/Her2+ or triple negative (TN).9. The method of claim 1 , wherein the non-Hodgkin lymphoma is diffuse large B-cell lymphoma.10. A method for achieving complete response claim 1 , partial response or stable disease claim 1 , as determined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in a patient claim 1 , comprising ...

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Номер записи: 35
25-04-2013 дата публикации

PYRAZOLOPYRIMIDINE DERIVATIVE

Номер: US20130102620A1
Автор: Aratake Seiji, Hemmi Kazuki, YAMAMOTO Keisuke
Принадлежит: KYOWA HAKKO KIRIN CO., LTD.

The invention provides a pyrazolopyrimidine derivative of formula (I), wherein, for example, Rrepresents —NRR(wherein Rand Rare the same or different and each is a hydrogen atom or aralkyl), Rrepresents formula (Ya) [wherein k and m each represents an integer of 0-2, n represents an integer of 0-4, L represents a single bond, Rrepresents halogen, Rrepresents aryl, X represents —CR(wherein Rrepresents a hydrogen atom), and Rrepresents a hydrogen], Rrepresents —SOR[wherein Rrepresents lower alkoxy, —NRC(═O)R(wherein Rrepresents a hydrogen atom, and Rrepresents lower alkyl)], and Rrepresents a hydrogen atom, or a pharmaceutically acceptable salt thereof. The invention also provides a medicament containing the pyrazolopyrimidine derivative, as well as a method of using the pyrazolopyrimidine derivative to prevent and/or treat skin diseases. 3. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Lis a single bond.4. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris aryl optionally having substituent(s).5. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris phenyl optionally having substituent(s).6. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris an aromatic heterocyclic group optionally having substituent(s).7. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom.8. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom claim 2 , and Ris lower alkyl optionally having substituent(s).9. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom claim 2 , and Ris COR(wherein Ris as defined ...

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Номер записи: 36
25-04-2013 дата публикации

NOVEL CONDENSED PYRIDINE OR CONDENSED PYRIMIDINE DERIVATIVE, AND MEDICINAL AGENT COMPRISING SAME

Номер: US20130102621A1
Автор: Inoue Noriyuki, Koshizawa Tomoaki, Morimoto Toshiharu, Ohgiya Tadaaki, Watanabe Gen, Yamasaki Nao
Принадлежит: KOWA CO., LTD.

The present invention relates to provision of a novel compound that has an activity of promoting insulin secretion from pancreatic β cells and thus is useful as a prophylaxis and/or therapeutic agent for diseases caused by hyperglycemia such as diabetes mellitus, and 3. The compound of claim 1 ,which is selected from the following compound group, or a salt thereof, or a solvate of the compound or the salt:tert-butyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;7-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;7-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]furo[3,2-d]pyrimidine-4-amine7-[1-(5-bromopyrimidin-2-yl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methyl sulfonyl)phenyl]-7-{1-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}furo[3,2-d]pyrimidine-4-amine;benzyl 4-(4-[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;isopropyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;ethyl 4-(4-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}furo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate;7-(1-{[3,5-bis(trifluoromethyl)phenyl]sulfonyl}piperidin-4-yl)-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;7-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-c]pyrimidine-4-amine;7-[1-(cyclohexylsulfonyl)piperidin-4-yl]-N-[2-fluoro-4-(methylsulfonyl)phenyl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-[1-(thiophen-2-ylsulfonyl)piperidin-4-yl]furo[3,2-d]pyrimidine-4-amine;N-[2-fluoro-4-(methylsulfonyl)phenyl]-7-{1-[(4-methoxyphenyl)sulfonyl]piperidin-4-yl}furo[3,2-d]pyrimidine-4-amine;7-[1-(butylsulfonyl) ...

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Номер записи: 37
25-04-2013 дата публикации

Tricyclic Compounds Having Cytostatic and/or Cytotoxic Activity and Methods of Use Thereof

Номер: US20130102623A1
Автор: Gangjee Aleem
Принадлежит:

The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders. 2. The compound according to claim 1 , wherein Y═NH; R═H; P═NR; R═H; X═NH; R═H; Z═S and R=a phenyl.3. The compound according to claim 1 , wherein Y═NH; R═H; P═NR; R═H; X═NH; R═H; Z═S; and R=a phenyl having a methyl substitution.4. The compound according to claim 3 , wherein the substitution on the phenyl is at the 4 position of the phenyl ring.6. The compound according to claim 5 , wherein Y═NH; R═H; P═NR; R═H; X═NH; R═H; Z═S; and R=a phenyl.8. The method according to claim 7 , wherein Y═NH; R═H; P═NR; R═H; X═NH; R═H; Z═S claim 7 , and R=a phenyl.9. The method according to claim 7 , wherein Y═NH; R═H; P═NR; R═H; X═NH; R═H; Z═S; and R=a phenyl having a methyl substitution.10. The method according to claim 9 , wherein the substitution on the phenyl is at the 4 position of the phenyl ring.11. The method according to claim 7 , wherein the route of administration of the compound of formula I is parenteral claim 7 , oral claim 7 , or intraperitoneal.12. The method according to claim 11 , wherein the parenteral route of administration is selected from the group consisting of intravenous; intramuscular; interstitial claim 11 , intraarterial; subcutaneous; intraocular; intracranial; intraventricular; intrasynovial; transepithelial claim 11 , including transdermal claim 11 , pulmonary via inhalation claim 11 , ophthalmic claim 11 , sublingual and bucal; topical claim 11 , including dermal claim 11 , ocular claim 11 , rectal and nasal inhalation via insufflation or nebulization.13. The method according to claim 7 , wherein the unit dosage is ...

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Номер записи: 38
25-04-2013 дата публикации

PHOTOCHROMIC MATERIAL

Номер: US20130102775A1
Автор: Horino Takeru, Oshima Toyoji, Tokita Atsuhiro
Принадлежит: MITSUBISHI GAS CHEMICAL COMPANY, INC.

The present invention is a photochromic material formed of a biimidazole compound represented by general formula (1-1): The present invention relates to a photochromic material, and more particularly, to a photochromic material formed of a novel biimidazole compound.Photochromic materials are typically materials that have a function (light modulation function) that enables them to reversibly change color (visible light transmittance) as a result of undergoing an isomerization reaction when irradiated with light, and not only materials prior to being irradiated with light, but also materials formed after being irradiated with light, are referred to as photochromic materials. Consequently, photochromic materials are used as eyeglasses for preventing glare, optical switches as well as display materials such as ink having the ability to switch between display and non-display status. In addition, research is also proceeding on their application to optical discs and other recording materials as well as holograms.Changes in color demonstrated by photochromic materials are typically expressed as a reversible chemical reaction of a material that is induced when the material is irradiated with light. Typical known examples of photochromic materials include spiropyran-based compounds, spirooxadine-based compounds, naphthopyran-based compounds, fulgide-based compounds, and diarylethene-based compounds (see, for example, Non-Patent Document 1). In addition, compounds having a novel structure that demonstrate rapid photoreactivity have also been recently reported (see, for example, Non-Patent Document 2).Photochromic materials are broadly divided into those that exhibit a phenomenon referred to as positive photochromism, which causes these materials to change from an uncolored form to a colored form (colored state) accompanying a structural change when irradiated with light, and those that exhibit a phenomenon referred to as negative photochromism (reverse photochromic materials ...

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Номер записи: 39
25-04-2013 дата публикации

PREPARATION OF 13-CYCLOHEXYL-3-METHOXY-6-[METHYL-(2--ETHYL)-CARBAMOYL]-7H-INDOLO-[2,1-a]-[2]-BENZAZEPINE-10-CARBOXYLIC ACID

Номер: US20130102777A1
Автор: Jean-Pierre-Andre Marc Bongartz, Patrick Hubert J. Nieste, Tom Cornelis Hortense Govaerts
Принадлежит: Janssen R&D Ireland ULC

The present invention relates to an improved method for the preparation of 13-cyclohexyl-3-methoxy-6-[methyl-(2-{2-[methyl-(sulphamoyl)-amino]-ethoxy}-ethyl)-carbamoyl]-7H-indolo-[2,1-a]-[2]-benzazepine-10-carboxylic acid. The present invention also relates to a new compound, namely tert-butyl (methyl-{2-[2-(methylamino)-ethoxy]-ethyl}-sulphamoyl)-carbamate, used in this improved method.

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Номер записи: 40
25-04-2013 дата публикации

PROCESSES AND INTERMEDIATES FOR PRODUCING AZAINDOLES

Номер: US20130102782A1
Автор: Jung Young Chun, Jurcik Václav, Kline Billie J., Looker Adam, Magdziak Derek, Olmo Beatriz Dominguez, Tanoury Gerald J.
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to processes and intermediates for the preparation of compounds useful as inhibitors of Janus kinases (JAK). 2. The process of claim 1 , wherein the organic solvent of step i) is an aprotic solvent.3. The process of claim 2 , wherein the aprotic solvent is acetonitrile claim 2 , toluene claim 2 , N claim 2 ,N-dimethylformamide claim 2 , N claim 2 ,N-dimethylacetamide claim 2 , acetone claim 2 , methyl tert-butyl ether claim 2 , or any combination thereof.4. The process of claim 1 , wherein the organic solvent of step i) is a protic solvent.5. The process of claim 4 , wherein the protic solvent is an alcohol selected from methanol claim 4 , propanol claim 4 , isopropanol claim 4 , butanol claim 4 , tert-butanol claim 4 , or any combination thereof.6. The process of claim 1 , wherein the base of step i) is an inorganic base.7. The process of claim 6 , wherein the inorganic base comprises tripotassium phosphate claim 6 , dipotassium hydrogen phosphate claim 6 , dipotassium carbonate claim 6 , disodium carbonate claim 6 , trisodium phosphate claim 6 , disodium hydrogen phosphate claim 6 , or any combination thereof.8. The process of claim 7 , wherein the inorganic base comprises an alkali metal hydroxide.9. The process of claim 8 , wherein the alkali metal hydroxide comprises NaOH claim 8 , KOH claim 8 , or any combination thereof.10. The process of claim 1 , wherein the transition metal catalyst of step i) is a palladium catalyst.11. The process of claim 10 , wherein the palladium catalyst of step i) comprises palladium(II)acetate claim 10 , tetrakis(triphenylphosphine)palladium(0) claim 10 , tris(dibenzylideneacetone)dipalladium(0) claim 10 , or any combination thereof.13. The process of claim 1 , wherein the reaction of step i) is performed at a temperature between about 50° C. and about 110° C.14. The process of claim 13 , wherein the reaction of step i) is performed at a temperature between about 60° C. and about 95° C.15. The process ...

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Номер записи: 41
02-05-2013 дата публикации

IMIDAZOPYRIDAZINE COMPOUNDS

Номер: US20130109661A1
Автор: Hermann Johannes Cornelius, Kuglstatter Andreas, Lucas Matthew C., Padilla Fernando, Wanner Jutta, Zhang Xiaohu
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to the use of novel compounds of formula I: 2. The compound of claim 1 , wherein A is pyridyl claim 1 , substituted with one or more A′.3. The compound of claim 2 , wherein B is phenyl.4. The compound of claim 3 , wherein A′ is pyrrolidinyl claim 3 , optionally substituted with one or more lower alkyl.5. The compound of claim 4 , wherein A′ is methylpyrrolidinyl or dimethylpyrrolidinyl.6. The compound of claim 3 , wherein A′ is lower alkoxy.7. The compound of claim 5 , wherein R is C(═O)NHR.8. The compound of claim 5 , wherein R is —C(═O)OH.9. The compound of claim 5 , wherein R is —NH(C═O)R.10. The compound of claim 3 , wherein n is 0 or two R together form a bicyclic heteroaryl or heterocycloalkyl ring system.11. The compound of claim 7 , wherein R1 is phenyl claim 7 , indolyl claim 7 , or indazolyl claim 7 , optionally substituted with one or more R.12. A compound selected from the group consisting of:(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(6-trifluoromethyl-pyridin-2-yl)-amine;(5-Ethyl-pyridin-2-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-6′-yl)-amine;(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(6-pyrrolidin-1-yl-pyridin-2-yl)-amine;[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;(1-tert-Butyl-1H-pyrazol-3-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;8-(2,2-Dimethyl-pyrrolidin-1-yl)-6-phenyl-imidazo[1,2-b]pyridazine;3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid methyl ester;3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;4-(3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoylamino)-benzoic acid;Sodium 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate;3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6- ...

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Номер записи: 42
02-05-2013 дата публикации

HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE

Номер: US20130109679A1
Автор: Boyer Stephen James, GAO Donghong Amy, GUO XIN, JR. Thomas Martin, KIRRANE, Sarko Christopher Ronald, SNOW Roger John, SOLEYMANZADEH Fariba, Zhang Yunlong
Принадлежит:

Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention. 1. A compound selected from the group consisting of:N-(2-methoxypyridin-4-yl)-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-cis-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4R)—N-{1-[3-(dimethylamino)propyl]-1H-benzimidazol-2-yl}-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;5-methyl-1-oxo-N-[1-(propan-2-yl)-1H-benzimidazol-2-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;(4R)—N-(1-benzyl-1H-pyrazol-4-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;(3S,4R)—N-(1-benzyl-1H-pyrazol-4-yl)-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4,4-dimethyl-N-(1-methyl-1H-benzimidazol-2-yl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-{1-[3-(dimethylamino)propyl]-1H-benzimidazol-2-yl}-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4-methyl-N-(1-methyl-1H-benzimidazol-2-yl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;(5R)-5-methyl-1-oxo-N-[1-(propan-2-yl)-1H-benzimidazol-2-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4] ...

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Номер записи: 43
02-05-2013 дата публикации

Naphthridine derivatives as PI3K inhibitors for the treatment of cancer and immune-inflammatory disease

Номер: US20130109688A1
Автор: Shuttleworth Stephen Joseph, Silva Franck Alexandre
Принадлежит: Karus Therapeutics Limited

Compounds of formulae (I) and (II): or a pharmaceutically acceptable salt thereof, wherein: Ris a nitrogen-containing 5 to 7-membered heteroaryl or heterocycle; Rand Rare each independently (LQ)Y, are described. The compounds are PI3K inhibitors and are useful for the treatment of cancer and immune-inflammatory diseases. 4. The compound according to claim 1 , wherein Ris H.5. The compound according to claim 1 , wherein Ris substituted aryl.6. The compound according to claim 5 , wherein Ris aryl substituted with at least one C-Chydroxyalkyl.7. The compound according to claim 1 , wherein Ris aryl substituted with at least one (NR)group.8. The compound according to claim 1 , wherein Ris (C-Calkylene)-NR-aryl.10. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable excipient.11. A method for treating cancer claim 1 , an immune disorder or an inflammatory disorder claim 1 , wherein said method comprises administering claim 1 , to a subject in need of such a treatment claim 1 , a compound according to .12. (canceled)13. The method according to claim 11 , wherein the cancer is a leukaemia or a PTEN-negative solid tumour.14. The method compound or composition according to claim 11 , wherein the immune disorder is organ rejection and the method is used to provide anti-rejection therapy to a subject following an organ transplant.15. Use of a compound as defined in claim 1 , for the manufacture of a medicament for use in therapy.16. (canceled) The present invention relates to 1,6-naphthyridines which act as inhibitors of PI3K, for the treatment of cancer, and immune-inflammatory diseases.The phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases involved in the regulation of a network of signal transduction pathways that control a range of cellular processes. PI3Ks are classified into three distinct subfamilies, named class I, II, and III based upon their substrate specificities. Class IA PI3Ks possess a ...

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Номер записи: 44
02-05-2013 дата публикации

DERIVATIVES OF PYRIDO [3,2-D] PYRIMIDINE, METHODS FOR PREPARATION THEREOF AND THERAPEUTIC USES THEREOF

Номер: US20130109693A1
Автор: Dehbi Oussama, Guillaumet Gérald, Routier Sylvain, Tikad Abdellatif
Принадлежит:

The present invention relates to a compound of the following general formula (I): 2. The compound of formula (I) according to claim 1 , wherein Ris selected from the group consisting of:hydrogen,halogens,(hetero)aryls comprising from 5 to 30 carbon atoms.3. The compound of formula (I) according to claim 1 , wherein Rrepresents a phenyl group.4. The compound of formula (I) according to claim 1 , wherein Rrepresents a phenyl group.5. The compound of formula (I) according to claim 1 , wherein Rrepresents a phenyl group substituted with a group OR claim 1 , R representing H or an alkyl group comprising from 1 to 10 carbon atoms.612.-. (canceled)13. The compound of formula (I) according to claim 1 , wherein Rrepresents H.14. The compound of formula (I) according to claim 1 , wherein Rrepresents H claim 1 , Rrepresents a phenyl group and Rrepresents a halogen or a phenyl group.15. The compound of formula (I) according to claim 1 , wherein Rrepresents H claim 1 , Rrepresents a phenyl group substituted with a group OR claim 1 , R representing H or an alkyl group claim 1 , comprising from 1 to 10 carbon atoms claim 1 , and Rrepresents a halogen or a phenyl group substituted with a group OR claim 1 , R representing H or an alkyl group comprising from 1 to 10 carbon atoms.17. The compound according to claim 1 , of the above formula (I-3) claim 1 , wherein Ris selected from the group consisting of the following groups:halogen,furanyl,thiophenyl,pyridyl,phenyl,benzothiazolyl, and{'sub': b', 'b, 'claim-text': phenyl,', 'pyridyl,', 'pyrimidinyl,', 'thiazolyl, and', 'isoxazolyl., 'a group —NHR″, R″being selected from the group consisting of the following groups18. The compound of formula (I) according to claim 1 , wherein Rrepresents NHBn.19. The compound of formula (I) according to claim 1 , wherein Rrepresents a —NH—(CH)—OH group.21. A method for treating or preventing diseases related to a deregulation of CDK1 claim 1 , CDK5 claim 1 , GSK3 and/or DYRK1A kinases comprising a step ...

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Номер записи: 45
02-05-2013 дата публикации

COMPOUNDS WITH ANTIBACTERIAL ACTIVITY AGAINST CLOSTRIDIUM

Номер: US20130109694A1
Автор: Guillemont Jérôme Emile Georges, Lounis Nacer, Raboisson Pierre Jean-Marie Bernard
Принадлежит: ELANCO ANIMAL HEALTH IRELAND LIMITED

The present invention is related to novel compounds of formula (I) having antibacterial activity against bacteria, in particular , pharmaceutical compositions comprising these compounds, and chemical processes for preparing these compounds. 112-. (canceled)14. The compound of claim 13 , or a pharmaceutically acceptable acid addition salt thereof claim 13 , or a solvate thereof claim 13 , having the (R)-configuration at the 4-position of the chromanyl moiety.15. The compound of claim 13 , or a pharmaceutically acceptable acid addition salt thereof claim 13 , or a solvate thereof claim 13 , wherein Rand Rare each halo.16. The compound of claim 14 , or a pharmaceutically acceptable acid addition salt thereof claim 14 , or a solvate thereof claim 14 , wherein Rand Rare each halo.17. The compound of claim 13 , or a pharmaceutically acceptable acid addition salt thereof claim 13 , or a solvate thereof claim 13 , wherein Rand Rare each bromo and are located at the 6- and 8-position of the chromanyl moiety.18. The compound of claim 16 , or a pharmaceutically acceptable acid addition salt thereof claim 16 , or a solvate thereof claim 16 , wherein Rand Rare each bromo and are located at the 6- and 8-position of the chromanyl moiety and wherein Rrepresents hydroxy.20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically active amount of a compound of claim 13 , or a pharmaceutically acceptable acid addition salt thereof claim 13 , or a solvate thereof.21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically active amount of a compound of claim 19 , or a pharmaceutically acceptable acid addition salt thereof claim 19 , or a solvate thereof.22. A method for treating a bacterial infection in a warm-blooded subject which comprises administering to the warm-blooded subject in need of such treatment a therapeutically effective amount of a compound of claim 13 , or a pharmaceutically ...

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Номер записи: 46
02-05-2013 дата публикации

TETRAHYDROCARBOLINE DERIVATIVE

Номер: US20130109699A1
Автор: Morimoto Takashi, Nakatani Shingo, Ohata Akira, Sugiyama Tetsuya
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

An object of the present invention is to provide a drug having the inhibitory activity on ENPP2 which is a different target from that of the existing drug, as a medicament useful in a urinary excretion disorder patient for whom the existing drug has the insufficient effect. 3. The compound according to , wherein Y is a straight C1-3 alkylene group optionally substituted with one or two Rs wherein Ris as defined in .4. The compound according to claim 3 , wherein X is a nitrogen atom.5. The compound according to claim 3 , wherein X is a carbon atom.6. The compound according to claim 4 , wherein Ris a hydrogen atom.8. The compound according to claim 7 , wherein Yis an unsubstituted methylene group claim 7 , and Tis a bond or an unsubstituted methylene group.9. The compound according to claim 7 , wherein the C5-10 bridged carbon ring in the C5-10 bridged carbon ring optionally substituted with one to five Rs is bicyclo[2.2.1]heptane or bicyclo[2.2.2]octane.10. The compound according to claim 7 , wherein the 5- to 7-membered monocycle in the 5- to 7-membered monocycle optionally substituted with one to five Rs is (i) a C5-7 monocyclic carbon ring or (ii) a 5- to 7-membered monocyclic heterocyclic ring containing one to four heteroatoms selected from an oxygen atom claim 7 , a nitrogen atom and a sulfur atom.11. The compound according to claim 10 , wherein the C5-7 monocyclic carbon ring is benzene claim 10 , cyclopentane or cyclohexane.14. The compound according to claim 7 , wherein the ring A is a C5-6 monocyclic carbon ring or a C9-10 bicyclic carbon ring.15. The compound according to claim 7 , wherein the ring A is (i) a 5- to 6-membered monocyclic heterocyclic ring containing one to four heteroatoms selected from an oxygen atom claim 7 , a nitrogen atom and a sulfur atom or (ii) a 9- to 10-membered bicyclic heterocyclic ring containing one to four heteroatoms selected from an oxygen atom claim 7 , a nitrogen atom and a sulfur atom.16. The compound according to claim ...

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Номер записи: 47
02-05-2013 дата публикации

TRISUBSTITUTED TRIAZOLOPYRIMIDINES FOR USE IN PLATELET AGGREGATION INHIBITION

Номер: US20130109702A1
Автор: Guile Simon, Hardern David, Ingall Anthony, Springthorpe Brian, Willis Paul
Принадлежит: AstraZeneca AB

The invention provides new triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation. 2. A compound according to in which Ris 3 claim 1 ,3 claim 1 ,3 claim 1 ,-trifluoropropyl claim 1 , butyl or propyl.3. A compound according to in which Ris phenyl or 4-fluorophenyl or 3 claim 1 ,4-difluorophenyl.4. A compound according to in which R is CHOH or OCHCHOH.5. A compound according to which is:[1R-[α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol:[1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;[1S-(1α,2α,3β(1S*,2R*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;[1R-[1α,2α,3β(1R*,2S*),5β]]-3-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2-(4-fluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol;[1S-(1α,2α,3β(1S*,2R*),5β]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;[1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2(3,4-difluorophenyl)cyclopropyl]-amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-triol;[1S-[1α,2α,3β(1S*,2R*),5β]]-3-[5-(Butylthio)-7-[(2-phenylcylopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxethoxy)-cyclopentane-1,2-diol; ...

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Номер записи: 48
02-05-2013 дата публикации

NEURODEGENERATIVE DISEASE THERAPEUTIC AGENT

Номер: US20130109714A1
Автор: Ariga Hiroyoshi
Принадлежит: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY

Provided is an unprecedented composition that is not a conventional symptomatic treatment, but makes possible the fundamental treatment of current neurodegenerative diseases by inhibiting oxidative-stress induced nerve-cell death. The disclosed neurodegenerative disease therapeutic agent includes a compound, or a salt of said compound, that inhibits oxidative-stress induced nerve-cell death to a high degree and is an agent used in the treatment of neurodegenerative diseases such as Parkinson's disease. 2. (canceled)3. The therapeutic agent for a neurodegenerative disease according to claim 1 , wherein m and n are 0.4. The therapeutic agent for a neurodegenerative disease according to claim 1 , wherein Ato Aare a single bond claim 1 , —O— claim 1 , —CO— claim 1 , —COO— claim 1 , —OCO— claim 1 , —O—CO—O— claim 1 , —NH— claim 1 , or —NH—COO—.5. The therapeutic agent for a neurodegenerative disease according to claim 1 , each independently of one another claim 1 , have a substituent claim 1 , and are Calkyl claim 1 , Calkenyl claim 1 , Calkynyl group claim 1 , Ccycloalkyl claim 1 , Caryl claim 1 , 5- to 10-membered heterocyclyl group comprising claim 1 , in addition to a carbon atom claim 1 , 1 to 4 heteroatoms selected from nitrogen atom claim 1 , oxygen atom claim 1 , and sulfur atom.6. The therapeutic agent for a neurodegenerative disease according to claim 1 , wherein at least one of -A-Rto -A-Ris a hydrogen atom claim 1 , a hydroxyl group claim 1 , or the following group which may have a substituent: a straight or branched chain Calkyl group claim 1 , a straight or branched chain Calkoxy group claim 1 , a straight or branched chain Calkyl-carbonyl group claim 1 , a straight or branched chain Calkoxy-carbonyl group claim 1 , a straight or branched chain Calkyl-carbonyloxy group claim 1 , a straight or branched chain Calkoxy-carbonyloxy group claim 1 , a Caryl group claim 1 , a 5- to 10-membered heterocyclyl group (comprising claim 1 , in addition to a carbon atom ...

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Номер записи: 49
02-05-2013 дата публикации

PROCESS FOR THE PREPARATION OF PYRIDO[2,1-a] ISOQUINOLINE DERIVATIVES BY CATALYTIC ASYMMETRIC HYDROGENATION OF AN ENAMINE

Номер: US20130109859A1
Автор: Abrecht Stefan, Scalone Michelangelo, Schmid Rudolf
Принадлежит: Hoffmann-La Roche Inc.

The invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula 2. The process according to claim 1 , characterized in that the asymmetric hydrogenation in step a) is performed with a transition metal catalyst selected from a ruthenium claim 1 , rhodium or iridium complex catalyst containing a diphosphine ligand.3. The process according to claim 1 , characterized in that the asymmetric hydrogenation in step a) is performed with a rhodium complex catalyst containing a diphosphine ligand.6. The process according to claim 1 , characterized in that the asymmetric hydrogenation in step a) is performed with a rhodium complex catalyst containing (S claim 1 ,R)-PPF-P(tBu)as chiral diphosphine ligand.7. The process according to claim 1 , characterized in that the asymmetric hydrogenation is carried out in an inert organic solvent.8. The process according to claim 8 , characterized in that the asymmetric hydrogenation is carried out in 2 claim 8 ,2 claim 8 ,2-trifluoroethanol.9. The process according to claim 1 , characterized in that the asymmetric hydrogenation takes place at a hydrogen pressure in a range from 1 bar to 200 bar.10. The process according to claim 1 , characterized in that the asymmetric hydrogenation takes place at a reaction temperature in a range from 20° C. to 120° C.11. The process according to claim 1 , characterized in that in step b) tert-butoxycarbonyl is introduced as amino protecting group.12. The process according to claim 1 , characterized in that the amidation in step c) is performed with formamide/sodium methoxide claim 1 , formamide/sodium ethoxide claim 1 , acetamide/sodium methoxide and acetamide/sodium ethoxide.13. The process according to claim 1 , characterized in that the amidation in step c) is performed in an organic solvent at temperatures of 10° C. to 70° C.14. A process for the preparation of (S)-1-((2S claim 1 ,3S claim 1 ,11bS)-2-amino-9 claim 1 ,10-dimethoxy-1 claim 1 ,3 claim 1 ,4 ...

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Номер записи: 50
09-05-2013 дата публикации

NOVEL [1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES

Номер: US20130116236A1
Автор: Adam Jean-Michel, Bissantz Caterina, Grether Uwe, Kimbara Atsushi, Nettekoven Matthias, Roever Stephan, Rogers-Evans Mark
Принадлежит: Hoffmann-La Roche Inc.

The invention relates to a compound of formula (I) 2. The compound of claim 1 , wherein A is alkyl or hydroxyalkyl.3. The compound of claim 1 , wherein A is selected from the group consisting of —CH— claim 1 , —CHCH— claim 1 , —CH(CH)— and —CH(OH)CH—.4. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , phenyl claim 1 , halophenyl claim 1 , alkoxyphenyl claim 1 , haloalkylphenyl claim 1 , haloalkoxyphenyl claim 1 , alkylsulfonylphenyl claim 1 , cyanophenyl claim 1 , cycloalkyl claim 1 , alkylheterocyclyl claim 1 , hydroxyheterocyclyl claim 1 , heteroaryl claim 1 , cycloalkylheteroaryl claim 1 , haloheteroaryl and alkylheteroaryl claim 1 , wherein said heterocyclyl is a carbocyclic ring containing at least one nitrogen atom and wherein said heteroaryl is pyridinyl claim 1 , pyrazolyl claim 1 , oxadiazolyl claim 1 , tetrazolyl or furazanyl.5. The compound of claim 1 , wherein Ris selected from the group consisting of haloalkyl claim 1 , phenyl claim 1 , halophenyl claim 1 , haloalkylphenyl claim 1 , cyanophenyl claim 1 , alkylsulfonylphenyl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , cycloalkylheteroaryl claim 1 , haloheteroaryl and alkylheteroaryl claim 1 , wherein said heteroaryl is pyridinyl claim 1 , pyrazolyl claim 1 , oxadiazolyl claim 1 , tetrazolyl or furazanyl.6. The compound of claim 1 , wherein Ris selected from the group consisting of chlorophenyl claim 1 , cyclohexyl claim 1 , dichlorophenyl claim 1 , pyridinyl claim 1 , chloropyridinyl claim 1 , dichloropyridinyl claim 1 , trifluoromethyl claim 1 , chlorodifluorophenyl claim 1 , trifluoromethylphenyl claim 1 , cyanophenyl claim 1 , phenyl claim 1 , methylsulfonylphenyl claim 1 , methyltetrazolyl claim 1 , methylfurazanyl and cyclopropyltetrazolyl.7. The compound of claim 1 , wherein one of Rand Ris hydrogen or ethyl and the other one is ethyl or cyclohexyl.8. The compound of claim 1 ...

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Номер записи: 51
09-05-2013 дата публикации

SUBSTITUTED IMIDAZOQUINOLINE DERIVATIVES AS KINASE INHIBITORS

Номер: US20130116248A1
Автор: Agarwal Veena R., Kumar Sanjay, Naik Nishigandha, SAHU Bichismita, Sharma Rajiv, Zahler Robert
Принадлежит: Piramal Enterprises Limited

The present invention relates to substituted imidazo[4,5-c]quinoline derivatives, the compounds of formula (I), wherein R, R, R, R, R, Rand Rare as defined in the specification, processes for their preparation, pharmaceutical compositions comprising compounds of formula (I), and their use in the treatment of diseases or disorders mediated by one or more kinases, particularly proliferative diseases or disorders such as cancer. These compounds can also be used in the treatment of inflammatory diseases and angiogenesis related disorders. 4. The compound according to claim 1 , wherein{'sub': 1', '6', '14', '1', '8', '6', '14', '1', '8, 'sup': 'a', 'Ris C-Caryl, heterocyclyl, heteroaryl or C-Calkylheterocyclyl, wherein each of C-Caryl, heterocyclyl, heteroaryl and C-Calkylheterocyclyl is optionally substituted with one or more of R;'}{'sub': '2', 'Ris nitro or —CN;'}{'sub': 3', '1', '8', '1', '8', 'x', 'y, 'Ris hydrogen or C-Calkyl, wherein C-Calkyl is optionally substituted with one or more groups selected from —CN or —NRR;'}{'sub': 4', '5', '7, 'R, Rand Rare hydrogen;'}{'sub': 6', '6', '14', '6', '14, 'sup': 'a', 'claim-text': [{'sup': a', 'b, 'sub': x', 'm', 'x', 'm', 'x', 'y', 'x', 'y', 'x', 'y', 'y', '2', 'x', 'y', 'x', 'y', 'x', '2', 'y', 'x', 'x', 'y', 'x', '8', 'x', 'y', '2', 'n', 'x', 'y', '2', '2', '2', 'x', '1', '8', '2', '8', '2', '8', '6', '14', '1', '8', '6', '14', '1', '8', '1', '8', '1', '8', '2', '8', '2', '8', '6', '14', '1', '8', '6', '14', '1', '8', '1', '8', '6', '14, 'Rat each occurrence is halogen, nitro, —CN, —OR, —S(═O)R, —S(═O)NRR, —NRR, —NRCOR, —N(COR), —NRCOOR, —NRSOR, —NRSOR, —NRCONRR, —COR, —COOR, —CONRR, —(CH)NRCOOR, -oxo-, —NHCHO(CH)OR, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Caryl, C-CalkylC-Caryl, heterocyclyl, C-Calkylheterocyclyl, heteroaryl or C-Calkylheteroaryl, wherein each of C-Calkyl, C-Calkenyl, C-Calkynyl, C-Caryl, C-CalkylC-Caryl, heterocyclyl, C-Calkylheterocyclyl, heteroaryl and C-CalkylheteroarylC-Caryl is optionally substituted ...

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Номер записи: 52
09-05-2013 дата публикации

INDOLIZINE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

Номер: US20130116249A1
Автор: Alcouffe Chantal, Herbert Corentin, Lassalle Gilbert
Принадлежит: SANOFI

The invention relates to compounds corresponding to formula (I): 2. The compound according to claim 1 , wherein Rrepresents an —OR claim 1 , —O-Alk-OR claim 1 , —COORor —O-Alk-COORgroup or a phenyl group optionally substituted with one or more alkyl or —COORgroups claim 1 , in which Rrepresents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms claim 1 , and Alk represents an alkylene chain containing 1 or 2 carbon atoms claim 1 , or a heteroaryl group.3. The compound according to claim 1 , wherein Rrepresents an —OR claim 1 , —O-Alk-ORor —O-Alk-COORgroup or a phenyl group optionally substituted with one or more alkyl or —COORgroups claim 1 , in which Rrepresents a hydrogen atom or a methyl group claim 1 , and Alk represents an alkylene chain containing 1 or 2 carbon atoms claim 1 , or a heteroaryl group.4. The compound of formula (I) according to claim 1 , wherein Rrepresents an alkyl group containing from 1 to 4 carbon atoms or a phenyl group.5. The compound of formula (I) according to claim 1 , wherein Rand Rtogether form claim 1 , with the carbon atoms of the phenyl nucleus to which they are attached claim 1 , a 6-membered nitrogenous heterocycle corresponding to one of formula (A) claim 1 , (B) or (C) defined above and in which:{'sub': a', '5', '5', '5', '5', '6', '7', '8', '5', '6', '5', '6', '5', '6', '5, 'Rrepresents a hydrogen atom or an alkyl or haloalkyl, —OR, -Alk-OR, -Alk′-COOR, —NRR, -Alk-NRR, -Alk-CN, —NR—COOR, -Alk′-CO—NRR, -Alk-CO—NR—ORor —O-Alk-COORgroup, or a heteroaryl, -Alk-heteroaryl or -Alk-aryl group in which the aryl or heteroaryl group is optionally substituted with an alkyl group or a halogen atom,'}{'sub': a′', '5, 'R represents a hydrogen atom or an alkyl or -Alk-ORgroup,'}{'sub': b', '5, 'Rrepresents a hydrogen atom or an alkyl or -Alk-COORgroup,'}{'sub': b′', '5, 'R represents a hydrogen atom or an alkyl, haloalkyl or -Alk-COORgroup,'}{'sub': c', '5', '5', '6', '7', '8, 'Rrepresents a hydrogen atom or an alkyl, —COOR ...

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Номер записи: 53
09-05-2013 дата публикации

IMIDAZOPYRIDINE DERIVATIVES, PROCESS FOR PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

Номер: US20130116250A1
Автор: Alcouffe Chantal, Herbert Corentin, Kirsch Reinhard, Lassalle Gilbert
Принадлежит: SANOFI

The invention relates to compounds corresponding to formula (I): 3. The compound according to , in which Rand Rtogether form , with the carbon atoms of the phenyl nucleus to which they are attached , a 6-membered nitrogenous heterocycle corresponding to either of formulae (A) and (B) as defined in , optionally in the form of a pharmaceutically acceptable salt thereof.4. The compound according to , in which Rand Rtogether form , with the carbon atoms of the phenyl nucleus to which they are attached , a 6-membered nitrogenous heterocycle corresponding to formula (A) as defined in , optionally in the form of a pharmaceutically acceptable salt thereof.6. The compound according to , in which Rrepresents a hydrogen atom or a —COOH , —CO—NH-Alk-NRRor —CO—NH-Alk-OH group , or else an alkyl group which is unsubstituted , in which Alk , Rand Rare as described in .7. The compound according to claim 1 , selected from the following compounds:6-(imidazo[1,5-a]pyridin-3-ylcarbonyl)-3-propylquinazoline-2,4(1H,3H)-dione,3-{3-[(2,4-dioxo-3-propyl-1,2,3,4-tetrahydroquinazolin-6-yl)carbonyl]imidazo[1,5-a]pyridin-1-yl}benzoic acid,3-[(2,4-dioxo-3-propyl-1,2,3,4-tetrahydroquinazolin-6-yl)carbonyl]imidazo[1,5-a]pyridine-6-carboxylic acid,3-(3-{[3-(4-fluorobenzyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl]carbonyl}imidazo[1,5-a]pyridin-1-yl)benzoic acid,3-{3 [(2,4-dioxo-3-propyl-1,2,3,4-tetrahydroquinazolin-6-yl)carbonyl]imidazo[1,5-a]pyridin-1-yl}benzamide,6-({1-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]imidazo[1,5-a]pyridin-3-yl}carbonyl-3-propylquinazoline-2,4(1H,3H)-dione,6-({1-[3-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]imidazo[1,5-a]pyridin-3-yl}carbonyl)-3-propylquinazoline-2,4(1H,3H)-dione,N-{3-[(2,4-dioxo-3-propyl-1,2,3,4-tetrahydroquinazolin-6-yl)carbonyl]imidazo[1,5-a]pyridin-1-yl}methanesulphonamide,2-morpholin-4-yl-ethyl 3-(3-{[3-(4-fluorobenzyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl]carbonyl}imidazo[1,5-a]pyridin-1-yl)benzoate,N-[2-(dimethylamino)ethyl]- ...

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Номер записи: 54
09-05-2013 дата публикации

COMPOUND FOR INHIBITING TYPE 5 PHOSPHODIESTERASE AND PREPARATION METHOD THEREOF

Номер: US20130116265A1
Автор: Zhang Nan, Zhong Rong
Принадлежит:

The present invention discloses a compound of formula (I) and citrate thereof as type 5 phosphodiesterase inhibitor, a preparation method thereof, and a pharmaceutical composition including the compound of formula (I) and citrate thereof. The experimental results of the present invention prove that the compound of formula (I) and citrate thereof can inhibit activity of type 5 phosphodiesterase, and can be used for treating erectile dysfunction, inhibiting platelet aggregation and treating thrombosis, decreasing pulmonary hypertension and treating cardiovascular diseases, treating asthma and treating diabetes gastroparesis. 3. A method of preparing the compound of claim 1 , the method comprising the following steps:(1) combining tetrahydrofuran and 2,6-lupetazin and di-tert-butyl dicarbonate, reacting at room temperature, and condensing the tetrahydrofuran to obtain 3,5-dimethyl-1-tert-butoxycarbonyl-piperazine;(2) adding tetrahydrofuran, kalium carbonicum, and methyl iodide to 3,5-dimethyl-1-tert-butoxycarbonyl-piperazine obtained in step (1), reacting at room temperature overnight, and then filtering and condensing to obtain a residue, adding water and dichloromethane to the residue, and extracting with dichloromethane to obtain an organic layer, merging the organic layer, rinsing with saturated brine, drying with anhydrous sodium sulfate, condensing to obtain a residue, and column chromatography of the residue with a solution of methanol and dichloromethane at a ratio of 1:20, to obtain 3,4,5-trimethyl-1-tert-butyl carbonyl piperazidine;(3) dissolving 3,4,5-trimethyl-1-tert-butyl carbonyl piperazidine obtained in step (2) in dioxane as a solvent, cooling, and slowly adding saturated hydrochloric acid dioxane solution drop by drop, stirring at room temperature, and then evaporating the dioxane solvent under reduced pressure to obtain 1,2,6-trimethyl piperazine;(4) dropping 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-ketone into ...

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Номер записи: 55
09-05-2013 дата публикации

Heterocyclic fused phenanthrolinone m1 receptor positive allosteric modulators

Номер: US20130116272A1
Автор: Jason W. Skudlarek, Scott D. Kuduk
Принадлежит: Individual

The present invention is directed to heterocyclic fused phenanthrolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

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Номер записи: 56
09-05-2013 дата публикации

BETA CARBOLINE DERIVATIVES USEFUL IN THE TREATMENT OF PROLIFERATIVE DISORDERS

Номер: US20130116273A1
Автор: Bruyere Celine, Frederick Raphael, Kiss Robert, Masereel Bernard, Reniers Jeremy, Wouters Johan
Принадлежит:

The invention provides novel beta-carboline derivatives of formulae (Ia) and (Ib) useful in the treatment of proliferative disorders including cancer, intermediates used in their preparation, processes for preparing the same and uses thereof. 2. The compound according to claim 1 , wherein Lis a direct bond claim 1 , methylene or ethylene claim 1 , and Ris cyclohexyl claim 1 , morpholinyl claim 1 , phenyl claim 1 , naphthalenyl or pyridyl claim 1 , each of said cyclohexyl claim 1 , morpholinyl claim 1 , phenyl claim 1 , naphthalenyl or pyridyl being optionally substituted with one or more substituents independently selected from halo claim 1 , hydroxy claim 1 , Calkyloxy claim 1 , cyano claim 1 , nitro or oxo or Ris Calkyl optionally substituted with one or more substituents independently selected from halo claim 1 , hydroxy claim 1 , Calkyl claim 1 , Calkyloxy claim 1 , cyano claim 1 , nitro or oxo; preferably wherein Lis methylene or ethylene and Ris phenyl optionally substituted with one or more substituents independently selected from halo or Ris benzoyl; or also preferably wherein Lis a direct bond and Ris Calkyl preferably methyl claim 1 , ethyl claim 1 , propyl claim 1 , butyl claim 1 , pentyl or hexyl claim 1 , each group being optionally substituted with one or more substituents independently selected from halo claim 1 , hydroxy claim 1 , Calkyloxy claim 1 , cyano claim 1 , nitro or oxo.3. The compound according to claim 1 , wherein Lis a direct bond claim 1 , methylene or ethylene claim 1 , and Ris cyclohexyl claim 1 , morpholinyl claim 1 , phenyl claim 1 , naphthalenyl or pyridyl claim 1 , each of said cyclohexyl claim 1 , morpholinyl claim 1 , phenyl claim 1 , naphthalenyl or pyridyl being optionally substituted with one or more substituents independently selected from halo claim 1 , hydroxy claim 1 , Calkyloxy claim 1 , cyano claim 1 , nitro or oxo; preferably wherein Lis methylene claim 1 , and Ris cyclohexyl or phenyl claim 1 , each of said cyclohexyl ...

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Номер записи: 57
16-05-2013 дата публикации

NOVEL CYCLIC AZABENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS

Номер: US20130123237A1
Автор: Anand Rajan, Apgar James M., Biftu Tesfaye, Chen Ping, Chu Lin, Colandrea Vincent J., Dong Guizhen, Dropinski James F., Feng Danqing, Hicks Jacqueline D., Jiang Jinlong, Kim Alexander J., Leavitt Kenneth J., Li Bing, Qian Xiaoxia, Sebhat Iyassu, Wei Lan, Wilkening Robert R., Wu Zhicai
Принадлежит: Merck Sharp & Dohme Corp.

Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 2. The compound according to wherein:{'sup': '3', 'T is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '1', 'U is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '2', 'V is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '4', 'W is selected from the group consisting of: CR, N and N-oxide,'}provided that at least one of T, U, V and W is N or N-oxide; [{'sub': '2', '(1) —CH—,'}, '(2) —CHF—,', {'sub': '2', '(3) —CF—,'}, '(4) —S—,', '(5) —O—,', {'sub': '2', '(6) —O—CH—,'}, '(7) —NH—,', '(8) —C(O)—,', '(9) —NHC(O)—,', '(10) —C(O)NH—,', {'sub': '2', '(11) —NHSO—,'}, {'sub': '2', '(12) —SONH—, and'}, {'sub': '2', '(13) —CO—,'}], 'X is absent or selected from{'sub': 2', '2', '1-6', '2', '2', '1-6', '1-6', '2', '1-6', '2', '2', '1-6', '1-6', '2, 'wherein each CHis unsubstituted or substituted with 1 or 2 substituents selected from: hydroxy, halogen, NH, Calkyl, COH, COCalkyl, COCalkyl, phenyl and —CH-phenyl, and wherein each NH is unsubstituted or substituted with 1 substituent selected from: Calkyl, COH, COCalkyl, COCalkyl, phenyl and —CH-phenyl;'} [{'sub': '3-10', '(1) Ccycloalkyl,'}, {'sub': '3-10', '(2) Ccycloalkenyl,'}, {'sub': '2-10', '(3) Ccycloheteroalkyl,'}, {'sub': '2-10', '(4) Ccycloheteroalkenyl,'}, '(5) aryl, and', '(6) heteroaryl,, 'Y is selected from{'sup': 'b', 'wherein cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R;'} (1) oxo,', '(2) —CN,', {'sub': '3', '(3) —CF,'}, {'sub': '1-6', '(4) —Calkyl,'}, {'sub': 2', 't, '(5) —(CH)- ...

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Номер записи: 58
16-05-2013 дата публикации

Pyrazolo Pyridine Derivatives as NADPH Oxidase Inhibitors

Номер: US20130123256A1
Автор: FIORASO-CARTIER LAETITIA, MOTTIRONI BIANCA, ORCHARD MIKE, PAGE PATRICK
Принадлежит: GENKYOTEX SA

The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase). 2. The pharmaceutical composition according to claim 1 , wherein Gis selected from phenyl claim 1 , 4-fluorophenyl claim 1 , 4-methoxyphenyl claim 1 , 4-nitrophenyl claim 1 , 2-chlorophenyl claim 1 , 2-methyl phenyl claim 1 , 4-(trifluoromethyl)phenyl claim 1 , 4-(trifluoromethoxy)phenyl claim 1 , 2 claim 1 ,5-difluorophenyl and 2-methoxyphenyl.3. The pharmaceutical composition according to claim 1 , wherein Gis optionally substituted alkyl.4. The pharmaceutical composition according to claim 1 , wherein Gis methyl.5. The pharmaceutical composition according to claim 1 , wherein Gis optionally substituted phenyl.6. The pharmaceutical composition according to claim 1 , wherein Gis selected from optionally substituted alkyl claim 1 , optionally substituted alkenyl and optionally substituted alkynyl.7. The pharmaceutical composition according to claim 1 , wherein Gis selected from optionally substituted aryl alkyl and optionally substituted heteroaryl alkyl.8. The pharmaceutical composition according to claim 1 , wherein G4 is selected from optionally substituted morpholinyl alkyl claim 1 , optionally substituted piperazinyl alkyl claim 1 , optionally substituted pyrrolidinyl alkyl and optionally substituted tetrahydrofuranyl alkyl.9. The pharmaceutical composition according to claim 1 , wherein G4 is selected from optionally substituted morpholinyl propyl claim 1 , optionally substituted morpholinyl ethyl claim 1 , optionally substituted piperazinyl ethyl claim 1 , optionally substituted pyrrolidinyl propyl and optionally substituted tetrahydrofuranyl methyl.10. The pharmaceutical composition according to claim 1 , selected from the following group:4-methyl-2-phenyl-5-(thiophen-2-ylmethyl)-1H- ...

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Номер записи: 59
16-05-2013 дата публикации

PYRIDO[3,4-B]INDOLES AND METHODS OF USE

Номер: US20130123277A1
Автор: CHAKRAVARTY Sarvajit, JAIN Rajendra Parasmal
Принадлежит: MEDIVATION TECHNOLOGIES, INC.

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[3,4-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in the variety of therapeutic application, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or neuronal disorder. 7. A compound selected from the group consisting of compounds 1 to 7 , J-1 to J-30 , K-1 to K-64 and L-1 to L-61 , or a pharmaceutically acceptable salt thereof.8. A pharmaceutical composition comprising (a) a compound of or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.9. A method of treating a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt thereof.10. (canceled)11. A kit comprising a compound according to or a pharmaceutically acceptable salt thereof and instructions for use in the treatment of a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder. This application claims priority to U.S. Provisional Patent Application No. 61/245,148, filed Sep. 23, 2009, the disclosure of which is hereby incorporated herein by reference in its entirety.Not applicable.Neurotransmitters such as histamine, serotonin, dopamine and norepinephrine mediate a large number of processes in the central nervous system (CNS) as well as outside the CNS. Abnormal neurotransmitter levels are associated with a wide variety of diseases and conditions including, but not limited to, Alzheimer's disease, Parkinson's Disease, autism, ADD, ADHD, Guillain-Barré syndrome, mild cognitive impairment, schizophrenia (such as cognitive impairment associated with ...

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Номер записи: 60
16-05-2013 дата публикации

POLYSUBSTITUTED DERIVATIVES OF 2-HETEROARYL-6-PHENYLIMIDAZO[1,2-a]PYRIDINES, AND PREPARATION AND THERAPEUTIC USE THEREOF

Номер: US20130123288A1
Автор: ALMARIO GARCIA Antonio, DE PERETTI Danielle, EVANNO Yannick, LARDENOIS Patrick, MACHNIK David, RAKOTOARISOA Nathalie
Принадлежит: SANOFI

Compounds of formula (I): 11. The method according to claim 1 , wherein the pathology is cerebral trauma or epilepsy.12. The method according to claim 1 , wherein the pathology is a psychiatric disease.13. The method according to claim 1 , wherein the pathology is an inflammatory disease.14. The method according to claim 1 , wherein the pathology is osteoporosis or cancer.15. The method according to claim 1 , wherein the pathology is Parkinson's disease claim 1 , Alzheimer's disease claim 1 , tauopathies or multiple sclerosis.16. The method according to claim 1 , wherein the pathology is schizophrenia claim 1 , depression claim 1 , substance dependence or an attention deficit hyperactivity disorder. This application is a divisional of U.S. patent application Ser. No. 12/881,815, filed Sep. 14, 2010, which is a continuation of International application No. PCT/FR2009/000303 filed Mar. 20, 2009, which are incorporated herein by reference in their entirety; and which claim the benefit of priority of French Patent Application No. 0801584 filed Mar. 21, 2008.The present invention relates to polysubstituted 2-heteroaryl-6-phenylimidazo[1,2-c]pyridine derivatives, to the preparation thereof and to the therapeutic use thereof in the treatment or prevention of diseases involving Nurr-1 nuclear receptors, also known as NR4A2, NOT, TINUR, RNR-1 and HZF3. The subject of the present invention is also the compounds of formula (I):in which:The compounds of formula (I) may comprise one or more asymmetrical carbon atoms. They may therefore exist in the form of enantiomers or of diastereoisomers. These enantiomers and diastereoisomers, and also mixtures thereof, including racemic mixtures, are part of the invention.The compounds of formula (I) may exist in the form of bases or of addition salts with acids. Such addition salts are part of the invention.These salts can be prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful for example, for ...

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Номер записи: 61
16-05-2013 дата публикации

LONIDAMINE ANALOGUES FOR FERTILITY MANAGEMENT

Номер: US20130123296A1
Автор: Chakrasali Ramappa, Georg Ingrid Gunda, Jakkaraj Sudhakar Rao, Roby Katherine, Tash Joseph S.
Принадлежит: The University of Kansas

Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject. 124.-. (canceled)26. A method as in claim 25 , wherein{'sub': '1', 'wherein Ris carboxyl, acryl, or carboxylic acid hydrazide; and'}{'sub': '2', 'wherein Ris halogen, alcohol, alkoxy, aralkyl, cycloalkyl, haloalkyl, haloalkoxy, amino, or carboxyl.'}27. A method as in claim 25 , wherein{'sub': '1', 'Rincludes one or more of a carboxylic acid, carboxylic acid ester, propionic acid, 2-methyl propionic acid, oxirane-carboxylic acid, cyclopropane carboxylic acid, propionic acid methyl ester, 2-methyl propionic acid methyl ester, oxirane-carboxylic acid methyl ester, or cyclopropane carboxylic acid methyl ester; and/or'}{'sub': '2', 'Rincludes a halogen, haloalkyl, or haloalkoxy.'}28. A method as in claim 25 , wherein the claim 25 , compound is selected from the group consisting of:3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid;6-chloro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazole-3-carboxylic acid methyl ester;6-fluoro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;3-[1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazol-3-yl]-acrylic acid;3-[1-(2,4-dichlorobenzyl)-6-chloro-1H-indazol-3-yl]-acrylic ...

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Номер записи: 62
16-05-2013 дата публикации

PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING OSTEOPOROSIS OR OBESITY COMPRISING PHENYLTETRAZOLE DERIVATIVE

Номер: US20130123297A1
Автор: BAE Myung-Ae, CHANG Sung Youn, HEO Jung Nyoung, HONG Jeong-Ho, Hwang Eun Sook, KANG Namsook, KIM Nak Jeong, Suh Jee Hee, Yi Kyu Yang, Yoo Sung-Eun
Принадлежит: KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

A pharmaceutical composition comprising a phenyltetrazole derivative of formula (I) or a pharmaceutical acceptable salt thereof is effective in preventing or treating osteoporosis, obesity, diabetes, or hyperlipidemia, by regulating protein TAZ. 2. The method of claim 1 , wherein the compound of formula (I) is methyl 2-butyl-6- styryl-1-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-benzimidazol-5-carboxylate; ormethyl 2-butyl-5-styryl-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-benzimidazol-6-carboxylate.4. The method of claim 3 , wherein the compound of formula (I) is selected from the group consisting of:{2-ethyl-7-methyl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridin-5-yl}methanol;2-butyl-5-methyl-6-pyridin-3-yl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine;methyl 2-butyl-6-pyridin-2-yl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine-5-carboxylate;{2-butyl-7-methyl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridin-5-yl}methanol;2-butyl-5-fluoromethyl-6-(1-oxypyridin-2-yl)-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine;(2-butyl-5-dimethoxymethyl-3-{2′-[1-(1-ethoxyethyl)-1H-tetrazol-5-yl]biphenyl-4-ylmethyl}-3H-imidazo[4,5-b]pyridin-6-yl)phenylmethanol;{2-butyl-5-dimethoxymethyl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridin-6-yl}phenylmethanol;6-bromo-2-butyl-3-{2′-[1-(1-ethoxyethyl)-1H-tetrazol-5-yl]biphenyl-4-ylmethyl}-3H-imidazo[4,5-b]pyridin-5-ylmethyl acetate;6-bromo-2-butyl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridin-5-ylmethyl acetate;2-butyl-7-methyl-5-((methylsulfanylmethoxy)methyl)-6-phenyl-3-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine;methyl 2-butyl-6-styryl-1-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-benzimidazol-5-carboxylate; andmethyl 2-butyl-5-styryl-1-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-benzimidazol-6-carboxylate. This application is a divisional ...

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Номер записи: 63
16-05-2013 дата публикации

PROCESS FOR THE PREPARATION OF THE COMPOUND OSI-906

Номер: US20130123501A1
Автор: "Obrien Andrew J.", Castelhano Arlindo L., Cutting Gary A., Locke Andrew J., Mulvihill Kristen Michelle, Norrie Robert, Park Stuart R., Rechka Josef A., Stevens Andrew MIchael, Thomas Christopher I.
Принадлежит:

Process for preparing the tyrosine kinase inhibitor OSI-906 comprises coupling Compound (2) with Compound (6) under specified conditions. 24-. (canceled)5. The process of claim 1 , wherein (e) further comprises filtering the liquid through activated charcoal.6. The process of claim 5 , wherein (e) further comprises treating the liquid with MTCf resin and/or MP-TMT resin.78-. (canceled)1115-. (canceled)16. The process of claim 1 , which results in at least about 10 kilograms of OSI-906 having a purity of at least about 90%.17. The process of claim 1 , having a yield of at least about 50% and providing OSI-906 as a material having a purity of at least about 98%.18. The process of claim 1 , which produces OSI-906 as a material containing less than 20 ppm palladium.19. The process of claim 1 , which provides OSI-906 having a particle size distribution of about D90<40 μm and about D50<15 μm.20. The process of claim 1 , wherein the isolating precipitate in (i) further comprises:(j) treating the precipitate with an acid in solution;(k) heating the solution; and(l) isolating an OSI-906 salt.2122-. (canceled)2426-. (canceled)27. The process of claim 23 , wherein reaction (m) is carried out at about 45-65 psi.2831-. (canceled)32. The process of claim 23 , having a yield of at least about 88% or more of Compound (2).3436-. (canceled)3841-. (canceled)4347-. (canceled) This application claims priority of U.S. Appl. No. 61/369,132, filed Jul. 30, 2010, the content of which is incorporated herein in its entirety by this reference.The present invention relates to chemical synthetic processes, and related intermediates and products, compositions, and uses thereof.The development of target-based anti-cancer therapies has become the focus of a large number of pharmaceutical research and development programs. Various strategies of intervention include targeting protein tyrosine kinases, including receptor tyrosine kinases believed to drive or mediate tumor growth.Insulin-like growth ...

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Номер записи: 64
16-05-2013 дата публикации

PROCESS FOR THE PREPARATION OF DIMIRACETAM

Номер: US20130123509A1
Автор: Farina Carlo, Gobbato Stefano, Roletto Jacopo
Принадлежит: NEUROTUNE AG

The invention relates to a method of manufacture of dimiracetam (2,5-dioxohexahydro-1 H-pyrrolo[1,2-a]imidazole), characterized in that a 4-oxo-butanoic acid ester is condensed with glycinamide in a one-pot reaction with a controlled pH. The reaction may be performed in aqueous solution or in an anhydrous lower alcohol solution. 115-. (canceled)17. The method of claim 16 , wherein the 4-oxo-butanoic acid ester (I) is condensed with glycinamide (II) or an acid addition salt thereof in aqueous solution.18. The method of claim 16 , wherein the 4-oxo-butanoic acid ester (I) is condensed with glycinamide (II) or an acid addition salt thereof in anhydrous lower alcohol solution.19. The method of claim 16 , wherein the 4-oxo-butanoic acid ester (I) is ethyl 4-oxobutanoate.20. The method of claim 16 , wherein the glycinamide (II) acid addition salt is glycinamide hydrochloride.21. The method of claim 17 , wherein the pH is kept within the range of pH 5.5 to 7.5.22. The method of claim 17 , wherein the reaction temperature is kept at around 100° C. for 0.5 to 10 h.23. The method of claim 22 , wherein the reaction temperature is kept at around 100° C. for 1 to 3 h.24. The method of claim 17 , wherein 1 to 3 molar equivalents of 4-oxobutanoic acid ester (I) are used for one mol equivalent of glycinamide (II).25. The method of claim 18 , wherein the lower alcohol is selected from the group consisting of methanol claim 18 , ethanol claim 18 , n-propanol claim 18 , iso-propanol claim 18 , n-butanol claim 18 , sec-butanol claim 18 , iso-butanol claim 18 , tert-butanol claim 18 , n-pentanol and iso-pentanol.26. The method of claim 25 , wherein the lower alcohol is n-propanol.27. The method of claim 18 , wherein ammonia is added in the final step of the reaction.28. The method of claim 18 , wherein the reaction temperature is kept at 90 to 120° C. for 2 to 10 h.29. The method of claim 27 , wherein the reaction temperature after addition of ammonia is kept at 30 to 90° C. for 10 to ...

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Номер записи: 65
23-05-2013 дата публикации

REMEDY FOR DIABETES

Номер: US20130130277A1
Автор: ARASHIDA Naoko, Fukuchi Naoyuki, Fukuda Yumiko, Ikenoue Takao, Miyanaga Wataru, OKAMOTO Satoru, Takayanagi Masaru, Takeshita Sen, YAMADA Naoyuki
Принадлежит: AJINOMOTO CO., INC.

A method of screening a compound having a hypoglycemic effect (hereinafter referred to as “hypoglycemic compound”), a remedy for diabetes which contains a compound having a novel function mechanism, etc. More specifically speaking, a method of screening a hypoglycemic compound capable of binding to the β subunit of a trimeric GTP-binding protein, a remedy for diabetes comprising a hypoglycemic compound, which is characterized by being capable of binding to the β subunit of a trimeric GTP-binding protein, as the active ingredient, etc. 16-. (canceled)7. A method for identifying a hypoglycemic compound , comprising:(A) fixing a trimeric GTP-binding protein β subunit (herein after referred to as “said protein”) to a solid phase;(B) contacting a test substance with the said protein; and(C) eluting a compound bound to the said protein in the step of (B) by using a solution containing a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof (herein after referred to as “said compound”), an acid, a base, or a denaturant.8. An antidiabetic agent comprising , as an active ingredient , a hypoglycemic compound capable of binding to a trimeric GTP-binding protein β subunit.9. An antidiabetic agent comprising , as an active ingredient , a hypoglycemic compound having a main effect of binding to a trimeric GTP-binding protein β subunit and enhancing an enzymatic activity of a phosphoinositide 3-kinase.10. An antidiabetic agent comprising , as an active ingredient , a compound capable of binding to the same site of a trimeric GTP-binding protein β subunit , where a compound represented by the general formula (I) binds to.11. A method for screening a hypoglycemic compound , characterized by detecting a compound capable of further enhancing a phosphoinositide 3-kinase enzymatic activity-enhancing effect of a trimeric GTP-binding protein β subunit.12. A method for screening a hypoglycemic compound , characterized by detecting a compound capable ...

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Номер записи: 66
23-05-2013 дата публикации

5,7-SUBSTITUTED-IMIDAZO[1,2-C]PYRIMIDINES AS INHIBITORS OF JAK KINASES

Номер: US20130131039A1
Автор: Boys Mark Laurence, Burgess Laurence E., Groneberg Robert D., Harvey Darren M., Huang Lily, Kercher Timothy, Kraser Christopher F., Laird Ellen, Tarlton Eugene, Zhao Qian
Принадлежит: ARRAY BIOPHARMA INC.

Compounds of Formula I: (Formula should be inserted here) and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R, R, R, R, R, R, R, Xand Xhave the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities. 2. (canceled)2. A compound according to claim 1 , wherein Ris hetAror hetAr.3. A compound according to claim 1 , wherein Ris hetAr.4. A compound according to claim 1 , wherein hetAris pyrazolyl claim 1 , thiazolyl claim 1 , oxazolyl claim 1 , thiadiazolyl claim 1 , imidazolyl claim 1 , pyrrolyl or thiophenyl optionally substituted with one or more substituents independently selected from (1-6C)alkyl claim 1 , fluoro(1-6C)alkyl claim 1 , difluoro(1-6C)alkyl claim 1 , trifluoro(1-6C)alkyl claim 1 , (1-4C alkoxy)(1-6C)alkyl claim 1 , trimethylsilyl(1-4C alkoxy)(1-6C)alkyl claim 1 , (3-6C)cycloalkyl claim 1 , a 4-6 membered oxacyclic ring claim 1 , hetCyc(1-2C)alkyl and hetAr(1-2C)alkyl.5. A compound according to claim 1 , wherein hetAris pyrazol-4-yl claim 1 , thiazol-5-yl claim 1 , imidazol-1-yl or 1 claim 1 ,3 claim 1 ,4-thiadiazol-2-yl optionally substituted with one or more substituents independently selected from methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , (2-isopropoxy)ethyl claim 1 , trimethylsilylethoxymethyl claim 1 , cyclobutyl claim 1 , oxetanyl claim 1 , 4-tetrahydro-2H-pyranyl claim 1 , (4-methylpiperazinyl)ethyl and pyrid-3-ylmethyl.6. A compound according to claim 1 , wherein hetAris pyrazol-4-yl optionally substituted with a substituent selected from methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , (2-isopropoxy)ethyl claim 1 , ...

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Номер записи: 67
23-05-2013 дата публикации

PYRAZOLE COMPOUNDS AS JAK INHIBITORS

Номер: US20130131043A1
Автор: Harrison Richard John, HOBSON ANDREW, Miller Warren, Oxenford Sally, Ramsden Nigel
Принадлежит:

The invention relates to compounds of formula (I) 2. A compound of claim 1 , wherein Ris Calkyl claim 1 , wherein Calkyl is optionally substituted with one or more halogen claim 1 , which are the same or different.3. A compound of claim 1 , wherein R claim 1 , Rare H.4. A compound of claim 1 , wherein Ris T; or Calkyl substituted with at least 1 R.5. A compound of claim 1 , wherein Ris T; CH-T; CH(CH)-T; CH(CHCH)-T; C(CH)-T; CH(CHCH(CH))-T; or CHCHT.6. A compound of claim 1 , wherein Ris Calkyl substituted with at least 1 R claim 1 , provided that Ris other than T.7. A compound of claim 1 , wherein Tis azetidine; piperidine; pyrrolidine; tetrahydropyran; cycloheptyl; cyclohexyl; or cyclopentyl and wherein Tis unsubstituted or substituted with one or more R claim 1 , which are the same or different.8. A compound of claim 1 , wherein Ris N(R)C(O)R; C(O)OR; C(O)N(RR); N(R)S(O)R; C(O)R; S(O)R; or Calkyl claim 1 , wherein Calkyl is optionally substituted with one or more R claim 1 , which are the same or different.9. A compound of claim 1 , wherein Ris N(R)S(O)R; C(O)R; or S(O)R.10. A compound of selected from the group consisting ofN-(1-Methyl-1H-pyrazol-4-yl)-1-((1-(methylsulfonyl)piperidin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;N-(3-(6-(1-methyl-1H-pyrazol-4-ylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)propyl)methanesulfonamide;N-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;N-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-1-((1-(methylsulfonyl)piperidin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;N-(1-methyl-1H-pyrazol-4-yl)-1-(piperidin-3-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;N-(1-methyl-1H-pyrazol-4-yl)-1-((1-methylpiperidin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;Rac-trans-N-(1-methyl-1H-pyrazol-4-yl)-1-(2-methylcyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;1-cyclohexyl-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine;N-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-4- ...

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Номер записи: 68
23-05-2013 дата публикации

NEW BICYCLIC COMPOUNDS AS PI3-K AND MTOR INHIBITORS

Номер: US20130131057A1
Автор: Alvarez Escobar Rosa Maria, Higueras Hernandez Ana Isabel, Martinez Gonzalez Sonia, Pastor Fernández Joaquin, Ramos Lima Francisco Javier, Rodriguez Hergueta Antonlo
Принадлежит: CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO

There is provided compounds of formula (I), wherein A, A, A, A, B, B, B, B, B, B, B, Band Rhave meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease. 3. The compound as claimed in claim 1 , wherein:{'sup': 1b', '10a', '11a', '10a', '1a', '1', '1a', '10a', '11a', '10a', '1b', '1b', '1', '1', '10a', '11a', '10a', '10a', '10a', '11a', '10a', '10a', '10a', '11a', '10a', '10a', '11a', '10a', '11a', '12a', '11a', '12a', '11a', '12a', '10a', '11a', '12a', '10a', '12a', '10a', '11a', '10a', '11a', '10a', '10a', '10a', '10a', '4a, 'sub': 2', '2', '2', '2', '2', '2, 'either (i) Ris present and represents —C(═Y)N(R)Ror —C(═Y)—Rand R(if present) represents hydrogen or Qas hereinbefore defined; or (ii) Ris present represents —C(═Y)N(R)Ror —C(═Y)—Rand either Ris not present or Ris present and represents hydrogen or Q, in which Qrepresents halo, —CN, —NO, —N(R)R, —OR, —C(═Y)—R, —C(═Y)N(R)R, —OC(═Y)—R, —OC(═Y)—OR, —OC(═Y)N(R)R, —OS(O)OR, —OP(═Y)(OR)(OR), —OP(OR)(OR), —N(R)C(═Y)R, —N(R)C(═Y)OR, —N(R)C(═Y)N(R)R, —NRS(O)R, —NRS(O)N(R)R, —S(O)N(R)R, —SC(═Y)R, —S(O)R, —SR, —S(O)R, aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from E); and/or'}{'sup': '3', 'Rrepresents substituted phenyl, optionally substituted indazolyl, pyrimidinyl, azaindolyl, indolyl or pyridyl.'}4. The compound as claimed in claim 1 , wherein: Rrepresents hydrogen claim 1 , chloro claim 1 , bromo claim 1 , iodo or —CN; each R claim 1 , R claim 1 , R claim 1 , Rand Rindependently represents hydrogen or Calkyl claim 1 , which alkyl group may by substituted by one or more substituents selected from ═O and E; or any relevant pair of Rand Rand/or Rand R claim 1 , may be linked ...

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Номер записи: 69
23-05-2013 дата публикации

1-Aryl or 1- Heteroaryl-Pyrido(B)indoles and Uses Thereof

Номер: US20130131070A1
Автор: Buolamwini John K.
Принадлежит:

Provided are 1-aryl or 1-heteroaryl substituted beta-carboline compounds or indole analogs thereof having the structure: 2. The substituted β-carboline compound of claim 1 ,wherein X is NH;{'sup': '1', 'Ris 1-naphthyl optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, C-Chaloalkoxy, —C(O)OC-Cester, —(C-C)—SO—NH—(C-C) sulfonamide, or phenyl;'}{'sup': 5', '6', '7', '2', '3', '4', '5', '6', '7', '2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'wherein, when one of R, R, or Ris C-Calkoxy, then R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Chaloalkoxy, —C(O)OC-Cester, —C-C—SO—NH—C-Csulfonamide, or phenyl such that at least two of R, R, R, R, R, and Rare other than H.'}3. The substituted β-carboline compound of claim 1 ,wherein X is NH;{'sup': '1', 'Ris 1-dihydroacenaphthenyl optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, phenyl, C-Chaloalkoxy, —C(O)OC-Cester, —(C-C)—SO—NH—(C-C) sulfonamide, or phenyl.'}4. The substituted β-carboline compound of claim 1 ,{'sub': '3', 'wherein X is N—CH, S, or O;'}{'sup': '1', 'Ris 1-naphthyl or 1-dihydroacenaphthenyl each optionally substituted with Br or F; and'}{'sup': 2', '3', '4', '5', '6', '7, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '1', '4, 'R, R, R, R, R, and Rare independently H, OH, halogen, CN, C-Calkyl, C-Calkoxy, phenyl, C-Chaloalkoxy, —C(O)OC-Cester, —C-C—SO—NH—C-Csulfonamide or phenyl.'}5. A pharmaceutical composition comprising the substituted β-carboline compound of and a pharmaceutically effective carrier.6. A method for inhibiting proliferation of cells associated with a cell proliferative ...

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Номер записи: 70
23-05-2013 дата публикации

PYRIDO[3,4-B]INDOLES AND METHODS OF USE

Номер: US20130131077A1
Автор: CHAKRAVARTY Sarvajit, DUGAR Sundeep, HUNG David T., JAIN Rajendra Parasmal, PROTTER Andrew Asher
Принадлежит: MEDIVATION TECHNOLOGIES, INC.

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[3,4-b]indoles are described, as are pharmaceutical-compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 124-. (canceled)26. The compound of claim 25 , or a pharmaceutically acceptable salt thereof claim 25 , wherein:{'sup': 7', '8', '9', '10', '4, 'Xis N; and each X, Xand Xis independently CR;'}{'sup': 8', '7', '9', '10', '4, 'Xis N; and each X, Xand Xis independently CR;'}{'sup': 10', '7', '8', '9', '4, 'Xis N; and each X, Xand Xis independently CR;'}{'sup': 7', '9', '8', '10', '4, 'each Xand Xis N; and each Xand Xis independently CR; or'}{'sup': 8', '10', '7', '9', '4, 'each Xand Xis N; and each Xand Xis independently CR.'}27. The compound of claim 26 , or a pharmaceutically acceptable salt thereof claim 26 , wherein:{'sup': 7', '8', '9', '10', '4, 'Xis N; and each X, Xand Xis independently CR.'}30. The compound of claim 25 , or a pharmaceutically acceptable salt thereof claim 25 , wherein q is 0.31. The compound of claim 25 , or a pharmaceutically acceptable salt thereof claim 25 , wherein each R claim 25 , R claim 25 , Rand Ris independently H claim 25 , hydroxyl claim 25 , C-Calkyl claim 25 , C-Cperhaloalkyl claim 25 , carboxy claim 25 , carbonylalkoxy claim 25 , or is taken together with the carbon to which it is attached and a geminal R claim 25 , R claim 25 , Ror Rto form a cycloalkyl moiety or a carbonyl moiety claim 25 , provided that at least one of R claim 25 , R claim 25 , Rand Ris other than H.32. The compound of claim 25 , or a pharmaceutically acceptable salt thereof claim 25 , wherein any one or more of (i)-(vii) apply claim 25 , provided that if any of provisions (ii) claim 25 , (iii) or (iv) applies claim 25 , only one of (ii) ...

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Номер записи: 71
23-05-2013 дата публикации

HIGH PENETRATION PRODRUG COMPOSITIONS OF 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE-RELATED COMPOUNDS AND USES THEREOF

Номер: US20130131100A1
Автор: Yu Chongxi
Принадлежит:

The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of 1H-imidazo[4,5-c]quinolin-4-amines and 1H-imidazo[4,5-c]quinolin-4-amine-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate. 2. A method for treating a condition in a biological subject claim 1 , comprising administrating to the biological subject a pharmaceutical composition comprising the high penetration composition according to and a pharmaceutically acceptable carrier.3. The method according to claim 1 , wherein the condition is selected from the group consisting of rheumatoid arthritis claim 1 , eczema claim 1 , psoriasis claim 1 , multiple sclerosis claim 1 , essential thrombocythaemia claim 1 , viral diseases and related condition claim 1 , and tumor and related condition.4. The method according to claim 3 , wherein the viral disease and related condition are selected from the group consisting of wart claim 3 , Actinic Keratosis claim 3 , flu claim 3 , hepatitis claim 3 , Severe Acute Respiratory Syndrome (SARS) claim 3 , pneumonia claim 3 , and acquired immunodeficiency syndrome (AIDS).5. The method according to claim 4 , wherein wart is selected from the group consisting of genital and perianal wart claim 4 , common wart ...

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Номер записи: 72
23-05-2013 дата публикации

SELECTIVE GLYCOSIDASE INHIBITORS

Номер: US20130131102A1
Автор: Borodkin Vladimir Sergeevich, Dorfmuller Helge, Van Aalten Daniel Marinus
Принадлежит: The University Court of the University of Dundee

The present invention provides glucoimidazole derivatives and methods of making them. The compounds can be used to inhibit the activity of O-GlcNAcase enzymes, including both bacterial OGA (bOGA) and human OGA (hOGA) and can be selective, showing low inhibition of hexosaminidases. The compounds can be used to study the role of the O-GlcNAcase modification in human or animal cells. Furthermore the compounds can have therapeutic uses in the treatment of diseases mediated by the activity of O-GlcNAcase enzymes including type II diabetes, Alzheimers Disease, and cancer. 2. The method of claim 1 , wherein Y of the compound of general formula I is —CHCH—.3. The method of claim 1 , wherein Z of the compound of general formula I is phenyl or substituted phenyl.4. The method of claim 1 , wherein YZ of the compound of general formula I is —CHCH—Z wherein Z is phenyl or substituted phenyl.5. The method of claim 1 , wherein n of the compound of general formula I is 1 and Ris a C-Csaturated or unsaturated aliphatic chain which may be branched.6. The method of claim 1 , wherein n of the compound of general formula I is 1 and Ris isopropyl.11. The method of claim 1 , wherein the condition is selected from the group consisting of Alzheimers disease claim 1 , diabetes and cancer.12. The method of claim 1 , wherein the condition is Alzheimers disease.13. The method of claim 1 , wherein the condition is diabetes.14. The method of claim 1 , wherein the condition is cancer. The present invention relates to compounds for the selective inhibition of glycosidase enzymes, methods of manufacture of the compounds, and the use of these compounds in the treatment of diseases or disorders responsive to inhibition of glycosidases.Many proteins in the eukaryotic cell are modified by O-linked N-acetylglucosamine (O-GlcNAc) on serines and threonines. O-GlcNAcylation has been shown to be important for regulation of the cell cycle, DNA transcription and translation, insulin sensitivity and protein ...

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Номер записи: 73
23-05-2013 дата публикации

CARBAZOLE LINKED PYRROLO[2,1-C][1,4]BENZODIAZEFINE HYBRIDS AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF

Номер: US20130131336A1
Автор: Kamal Ahmed, Reddy Adla Malla, Reddy Srinivasa K., Shetti Rajesh V.C.R.N.C.
Принадлежит:

The present invention provides a compound of general formulae A useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formulae 6a-g, 10a-o, 14a-g and 18a-o. 3. Carbazole linked pyrrolo[2 claim 1 ,1-c][1 claim 1 ,4]benzodiazepine hybrids as claimed in is represented by the group of the following compounds:7-methoxy-8-[3-(9H-9-carbazoly)propyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6a,7-methoxy-8-[4-(9H-9-carbazoly)butyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6b,7-methoxy-8-[5-(9H-9-carbazoly)pentyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6c,7-methoxy-8-[6-(9H-9-carbazoly)hexyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6d,7-methoxy-8-[7-(9H-9-carbazoly)heptyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6e,7-methoxy-8-[8-(9H-9-carbazoly)octyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6f,7-methoxy-8-[9-(9H-9-carbazoly)nonyloxy]-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 6g,7-methoxy-8-{3-[3,6-di-phenyl-9H-9-carbazoly]propyloxy]]}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 10a,7-methoxy-8-{4-[3,6-d]-phenyl-9H-9-carbazoly]butyloxyl]}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 10b,7-methoxy-8-{5-[3,6-di-phenyl-9H-9-carbazoly]pentyloxy}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 10c,7-methoxy-8-{3-[3,6-di(4-methoxyphenyl)-9H-9-carbazoly]propyloxy]}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 10d,7-methoxy-8-{4-[3,6-di(4-methoxyphenyl)-9H-9-carbazoly]butyloxyl]}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 10e,7-methoxy-8-{5-[3,6-di(4-methoxyphenyl)-9H-9-carbazoly]pentyloxy}-(11aS)-1,2 ...

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Номер записи: 74
30-05-2013 дата публикации

HERBICIDAL COMPOUNDS

Номер: US20130137574A1
Автор: CARTER Neil Brian, CORDINGLEY, Crowley Patrick Jelf, TURNBULL Michael Drysdale, V Matthew Robert
Принадлежит: SYNGENTA LIMITED

The present invention relates to a method of controlling plants or inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I) 4. A herbicidal composition which comprises a herbicidally effective amount of a compound of formula (Ib) as defined in in addition to formulation adjuvants.5. A herbicidal composition which comprises a herbicidally effective amount of a compound of formula (Ib) as defined in claim 1 , optionally one or more further herbicides claim 1 , and optionally one or more safeners. This application is a divisional of U.S. application Ser. No. 12/863,286, filed on Jul. 16, 2010, which is a U.S. National Stage under 35 U.S.C. §371 of International Application No. PCT/GB2009/000127 filed Jan. 16, 2009, which claims priority to GB 0800856.7 filed Jan. 17, 2008, the contents of which are incorporated herein by reference the contents of which are incorporated herein by reference.The present invention relates to novel herbicidal pyrido[2,3-b]pyrazines, to processes for their preparation, to compositions comprising these compounds, and to their use in controlling plants or in inhibiting plant growth.Pyrido[2,3-b]pyrazines were disclosed as intermediates in the synthesis of fungicidal compounds, for example, in WO 04/056825, WO 05/123698 and WO 05/123733. Pyrido[2,3-b]pyrazines were disclosed as fungicidal compounds in WO 05/010000.It has now surprisingly been found that certain pyrido[2,3-b]pyrazines display excellent herbicidal and growth-inhibiting properties.The present invention therefore provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I)wherein Rand Rare independently hydrogen, C-Calkyl, C-Chaloalkyl, halo, cyano, hydroxy, C-Calkoxy, C-Calkylthio, aryl or aryl substituted by one to five R, which may be the same or different, or heteroaryl or heteroaryl ...

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Номер записи: 75
30-05-2013 дата публикации

OXOPYRAZINE DERIVATIVE AND HERBICIDE

Номер: US20130137577A1
Автор: Ito Minoru, Kobayashi Masami, Mitsunari Takashi, Nakano Yuki, Tamai Ryuji
Принадлежит:

The present invention is to provide an oxopyrazine derivative having an excellent herbicidal activity and besides exhibiting high safety for useful crops and the like, or a salt thereof, and a herbicide containing the same. 2. (canceled)3. (canceled)4. The oxopyrazine derivative or the agrochemically acceptable salt thereof according to claim 1 , wherein Ris hydroxyl group; or OM (wherein M is an alkali metal cation or an ammonium cation).5. The oxopyrazine derivative or the agrochemically acceptable salt thereof according to claim 1 , wherein{'sup': '2', 'Xis a nitrogen atom;'}{'sup': 1', '6', '7', '8', '1', '9', '10', '11', '12', '1', '13, 'sub': 1', '12', '2', '6', '2', '6', '3', '8', '1', '6', '2', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '6', '10', '1', '6', '1', '6', '6', '10, 'Rrepresents a hydrogen atom; a C-Calkyl group; a C-Calkenyl group; a C-Calkynyl group; a C-Ccycloalkyl group; a C-Chaloalkyl group; a C-Chaloalkenyl group; a C-Calkylthio-C-Calkyl group; a C-Calkylsulfonyl-C-Calkyl group; a C-Calkoxy-C-Calkyl group; a C-Calkoxy-C-Calkoxy-C-Calkyl group; a phenoxy-C-Calkyl group; a C-Chaloalkoxy-C-Calkyl group; a tetrahydrofuran-C-Calkoxy-C-Calkyl group; a C-Calkylsulfonyl-C-Calkoxy-C-Calkyl group; a cyano-C-Calkoxy-C-Calkyl group; a cyano-C-Calkyl group; a C-Calkylcarbonyloxy-C-Calkyl group; a C-Cacyl-C-Calkyl group; a C-Calkoxycarbonyl-C-Calkyl group; a (RRN—C═O)—C-Calkyl group; a C-Caryl-C-Calkyl group (the aryl moiety of the group may be substituted with one or two or more identical or different Rs); a Het-C-Calkyl group (the group may be substituted with one or two or more identical or different Rs); a NRRgroup; a C-Caryl group (the group may be substituted with one or two or more identical or different Rs); or a ...

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Номер записи: 76
30-05-2013 дата публикации

ANTICANCER DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

Номер: US20130137659A1
Автор: COMMERCON Alain, Gauzy-Lazo Laurence, Hubert Philippe
Принадлежит: SANOFI

Provided herein are compounds of formula (I): 2. The compound according to in which U═U′ and/or W═W′ and/or R═R′ and/or R═R′ and/or Y═Y′ and/or the two groups ALK and ALK′ attached to the phenyl or pyridyl nucleus are identical.5. The compound according to in which Y and Y′ represent a group (C-C)alkoxy.6. The compound according to in which M represents N.7. The compound according to in which if Lrepresents a single bond claim 1 , Lrepresents —(CHCHO)—CHCH— or —(CHCHO)—CHCHNR″—(C-C)ALK-.8. The compound according to in which G represents a group —OH claim 1 , —O(C-C)alkyl claim 1 , —NH claim 1 , —NH(C-C)alkyl or —N(C-C)alkylor G represents a group —NRR′ in which R and R′ form claim 1 , together with the nitrogen atom to which they are attached claim 1 , a group (C-C)heterocycloalkyl which may comprise in the ring another heteroatom chosen from N claim 1 , O and S and which may be optionally substituted with at least one substituent chosen from a group (C-C)alkyl claim 1 , a halogen atom and a hydroxyl group.9. The compound according to in which:{'sub': 1', '1', '6', '2', '6', '6, 'L=-D-(C-C)ALK- and L=-(C-C)ALK-; or'}{'sub': 1', '2', '2', 'i', '2', '1', '6, 'L=-(OCHCH)— and L=-(C-C)ALK-; or'}{'sub': 1', '2', '2', '2', 'j', '2', '2', '1', '6, 'L=single bond and L=-(CHCHO)—CHCHNR″—(C-C)ALK-; or'}{'sub': 1', '1', '6', '2', '2', '2', 'j', '2', '2', '1', '6, 'L=-D-(C-C)ALK-, and L=-(CHCHO)—CHCHNR″—(C-C)ALK-; or'}{'sub': 1', '1', '6', '2', '2', '2', 'j', '2', '2, 'L=-D-(C-C)ALK- and L=-(CHCHO)—CHCH—.'}10. The compound according to in which:{'sub': 1', '1', '6', '2', '1', '6', 'a, 'L=-D-(C-C)ALK-, L=-(C-C)ALK-, Q=single bond, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '1', '6', '2', '1', '6', 'a, 'L=-D-(C-C)ALK-, L=-(C-C)ALK-, Q=CO, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '2', '2', 'i', '2', '1', '6', 'a, 'L=-(OCHCH)—, L=-(C-C)ALK-, Q=single bond, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '2', '2', 'i', '2', '1', '6', 'a, 'L=-(OCHCH)—, L=-(C-C)ALK-, Q=CO, k=1-10, G=OR, RCG1=-SZ;'}{'sub': ...

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Номер записи: 77
30-05-2013 дата публикации

NOVEL [1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES

Номер: US20130137676A1
Автор: Bissantz Caterina, Grether Uwe, Kimbara Atsushi, Nettekoven Matthias, Roever Stephan, Rogers-Evans Mark
Принадлежит: Hoffmann-La Roche Inc.

The invention relates to a compound of formula (I) 2. The compound according to claim 1 , wherein A is selected from the group consisting of alkylene claim 1 , —CHC(O)— and a bond.3. The compound according to claim 1 , wherein A is alkylene.4. The compound according to any claim 1 , wherein A is selected from the group consisting of methylene claim 1 , ethylene and —CH(CH)—.5. The compound according to claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , haloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , phenyl claim 1 , halophenyl claim 1 , alkoxyphenyl claim 1 , haloalkylphenyl claim 1 , haloalkoxyphenyl claim 1 , cyanophenyl claim 1 , cycloalkyl claim 1 , heterocyclyl claim 1 , haloheteroaryl and alkylheteroaryl claim 1 , wherein said heterocyclyl is oxetanyl and said heteroaryl is pyridinyl or furazanyl.6. The compound according to claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , haloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , phenyl claim 1 , halophenyl claim 1 , alkoxyphenyl claim 1 , haloalkylphenyl claim 1 , haloalkoxyphenyl claim 1 , cyanophenyl claim 1 , cycloalkyl claim 1 , oxetanyl claim 1 , pyridinyl claim 1 , halopyridinyl and alkylfurazanyl.7. The compound according to claim 1 , wherein Ris selected from the group consisting of trifluoromethyl claim 1 , phenyl claim 1 , chlorophenyl claim 1 , bromophenyl claim 1 , cyanophenyl claim 1 , cyclohexyl claim 1 , pyridinyl claim 1 , chloropyridinyl claim 1 , methylfurazanyl and trifluoromethylphenyl.8. The compound according to claim 1 , wherein Ris alkyl.9. The compound according to claim 1 , wherein Ris tert.-butyl.10. The compound according to claim 1 , wherein Ris —NRR.11. The compound according to claim 1 , wherein Rand Rtogether with the nitrogen atom to which they are attached form morpholinyl claim 1 , halopyrrolidinyl or hydroxypyrrolidinyl.12. The compound according to claim 1 , wherein Rand Rtogether with the nitrogen atom to which ...

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Номер записи: 78
30-05-2013 дата публикации

HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS

Номер: US20130137681A1
Автор: Arvanitis Argyrios G., Falahatpisheh Nikoo, Fridman Jordan S., Jalluri Ravi Kumar, JR. Thomas P., Maduskuie, Rafalski Maria, Rodgers James D., Shepard Stacey, Storace Louis, Vaddi Krishna, Wang Haisheng
Принадлежит: INCYTE CORPORATION

The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases. 2. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein X is N.3. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein X is CR.4. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ais C.5. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ais N.6. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ais C.7. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ais N.8. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein at least one of A claim 1 , A claim 1 , U claim 1 , T claim 1 , and V is N.10. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein n is 0.11. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein n is 1.12. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein n is 1 and Y is Calkylene claim 1 , Calkenylene claim 1 , (CRR)C(O)(CRR) claim 1 , (CRR)C(O)NR(CRR) claim 1 , (CRR)C(O)O(CRR) claim 1 , (CRR)OC(O)(CRR) claim 1 , wherein said Calkylene or Calkenylene claim 1 , is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 halo claim 1 , OH claim 1 , CN claim 1 , amino claim 1 , Calkylamino claim 1 , or Cdialkylamino.13. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein n is 1 and Y is Calkylene claim 1 , (CRR)C(O)(CRR) claim 1 , (CRR)C(O)NR(CRR) claim 1 , (CRR)C(O)O(CRR) claim 1 , ...

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Номер записи: 79
30-05-2013 дата публикации

PYRIDO[3,4-B]INDOLES AND METHODS OF USE

Номер: US20130137705A1
Автор: CHAKRAVARTY Sarvajit, JAIN Rajendra Parasmal
Принадлежит:

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[3,4-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 7. A compound selected from the group consisting of compounds 1 to 7 , J-1 to J-30 , K-1 to K-64 and L-1 to L-61 , or a pharmaceutically acceptable salt thereof.8. A pharmaceutical composition comprising (a) a compound of or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.9. A method of treating a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt thereof.10. (canceled)11. A kit comprising a compound according to or a pharmaceutically acceptable salt thereof and instructions for use in the treatment of a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder. This application claims priority to U.S. Provisional Patent Application No. 61/245,148, filed Sep. 23, 2009, the disclosure of which is hereby incorporated herein by reference in its entirety.Not applicable.Neurotransmitters such as histamine, serotonin, dopamine and norepinephrine mediate a large number of processes in the central nervous system (CNS) as well as outside the CNS. Abnormal neurotransmitter levels are associated with a wide variety of diseases and conditions including, but not limited to, Alzheimer's disease, Parkinson's Disease, autism, ADD, ADHD, Guillain-Barré syndrome, mild cognitive impairment, schizophrenia (such as cognitive impairment associated with ...

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Номер записи: 80
30-05-2013 дата публикации

PYRAZOLOPYRIMIDINE PDE 10 INHIBITORS

Номер: US20130137707A1
Автор: Cox Christopher D., Raheem Izzat T., Schreier John D.
Принадлежит:

The present invention is directed to pyrazolopyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction. 6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHCHCH— or —CH-cyclopropyl- claim 1 , which is substituted with a substituent selected from the group consisting of:{'sub': '1-6', '(1) Calkyl, which is unsubstituted or substituted with halogen or hydroxyl,'}{'sub': '1-6', '(2) —O—Calkyl, which is unsubstituted or substituted with halogen or hydroxyl,'}{'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6, '(3) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, —NH, —NH—Calkyl, or —N(Calkyl)(Calkyl), —O—Calkyl or Calkyl, which is unsubstituted or substituted with fluoro,'}{'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6, '(4) heteroaryl, which is unsubstituted or substituted with halogen, hydroxyl, —NH, —NH—Calkyl, or —N(Calkyl)(Calkyl), —O—Calkyl or Calkyl, which is unsubstituted or substituted with fluoro,'}{'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6, '(5) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, —NH, —NH—Calkyl, or —N(Calkyl)(Calkyl), —O—Calkyl or Calkyl, which is unsubstituted or substituted with fluoro, and'}{'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6, '(6) —O-heteroaryl, which is unsubstituted or substituted with halogen, hydroxyl, —NH, —NH—Calkyl, or —N(Calkyl)(Calkyl), —O—Calkyl or Calkyl, which is unsubstituted or substituted with fluoro.'}8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.12. A pharmaceutical composition which comprises a pharmaceutically acceptable ...

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Номер записи: 81
30-05-2013 дата публикации

METHODS AND COMPOSITIONS FOR KINASE INHIBITION

Номер: US20130137708A1
Автор: Garske Adam L., Shokat Kevan M.
Принадлежит: The Regents of the University of California

The present invention sets forth a new chemical genetic approach for engineering kinase enzymes with a cysteine gatekeeper residue as well as for developing electrophilic inhibitors thereto. The present invention also provides a Src proto-oncogenic tyrosine kinase with a cysteine gatekeeper that recapitulates wild type activity and can be irreversibly inhibited both in vitro and in cells. The present invention also provides methods and compositions for modulating kinases and for treating kinase-associated diseases. 3. The compound of claim 2 , wherein L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , and Lare claim 2 , in each instance claim 2 , independently a bond claim 2 , —NH— claim 2 , or substituted or unsubstituted C-Calkylene.4. The compound of claim 2 , wherein Lis a bond claim 2 , —NH— claim 2 , or unsubstituted C-Calkylene.6. The compound of claim 5 , wherein at least one -L-Ris an electrophilic moiety.7. The compound of claim 6 , wherein{'sup': '3', 'Lis a bond, —NH—, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene; and'}{'sup': '3', 'Ris a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or halogen.'}8. The compound of claim 6 , wherein{'sup': '3', 'sub': 2', '2, 'Lis —C(O)—, —S(O)—, —NHC(O)—, or —NHS(O)—; and'}{'sup': '3', 'Ris unsubstituted alkyl or alkyl substituted with chloro, fluoro, methyl, difluoromethyl, or trifluoromethyl.'}9. The compound of claim 8 , wherein Ris ethenyl claim 8 , ethyl claim 8 , 2 claim 8 ,2 claim 8 ,2-trichloroethyl claim 8 , 2 claim 8 ,2-dichloroethyl claim 8 , 2-chloroethyl claim 8 , 2 claim 8 ,2 claim 8 ,2-trifluoroethyl claim 8 , 2 claim 8 ,2-difluoroethyl claim 8 , or 2-fluoroethyl claim 8 , propyl claim 8 , isopropyl claim 8 , 1-propenyl claim 8 , or 2-propenyl.11. The compound of claim 1 , wherein claim 1 ,{'sup': '1', 'Lis a bond; and'}{'sup': '1', 'sub': '2', 'Ris hydrogen or NH.'}12. The compound of claim 11 , wherein claim 11 ,{'sup': '1 ...

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Номер записи: 82
30-05-2013 дата публикации

Compounds that modulate EGFR activity and methods for treating or preventing conditions therewith

Номер: US20130137709A1
Автор: Gray Nathanael S., Zhou Wenjun
Принадлежит:

Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith. 2. The compound of claim 1 , wherein Xis NH.3. The compound of claim 1 , wherein Ris —H claim 1 , —CH claim 1 , —OCH claim 1 , —OCHCH claim 1 , or —OCH(CH).4. The compound of claim 1 , wherein Z is —(CH)NRC(O)R claim 1 , wherein Ris hydrogen and Ris C-Calkenyl.6. The compound of claim 5 , wherein Ris fluorine claim 5 , chlorine claim 5 , bromine claim 5 , or methyl.7. The compound of claim 5 , wherein Ris chlorine.10. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.11. A method for inhibiting a kinase claim 1 , comprising contacting the kinase with an effective amount of a compound of .12. The method of claim 11 , wherein the kinase comprises a cysteine residue.13. The method of claim 11 , wherein the kinase is EGFR.14. The method of claim 12 , wherein the cysteine residue is located in or near the position equivalent to Cys 797 in EGFR.15. The method of claim 11 , wherein the kinase comprises EGFR claim 11 , Jak3 claim 11 , Blk claim 11 , Bmx claim 11 , Btk claim 11 , HER2 (ErbB2) claim 11 , HER4 (ErbB4) claim 11 , Itk claim 11 , Tec claim 11 , or Txk.16. The method of claim 13 , wherein the EGFR is a mutant EGFR.17. The method of claim 16 , wherein the EGFR mutation comprises G719S claim 16 , G719C claim 16 , G719A claim 16 , L858R claim 16 , L861Q claim 16 , an exon 19 deletion mutation or an exon 20 insertion mutation.18. The method of claim 17 , wherein the EGFR mutation further comprises an EGFR T790M claim 17 , T854A or D761Y resistance mutation.19. A method of inhibiting EGFR in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound of .20. The method of claim 19 , wherein the EGFR is a Her-kinase.2157.-. (canceled) This application claims the benefit of U.S. provisional application Ser. Nos. 61/331,647, filed May 5, 2010, and 61/426,961, filed Dec. 23, 2010 ...

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Номер записи: 83
06-06-2013 дата публикации

PHARMACEUTICAL COMPOSITIONS OF 7-(6-(2-HYDROXYPROPAN-2-YL)PYRIDIN-3-YL)-1-((TRANS)-4-METHOXYCYCLOHEXYL)-3,4-DIHYDROPYRAZINO [2,3-B]PYRAZIN-2(1H)-ONE, A SOLID FORM THEREOF AND METHODS OF THEIR USE

Номер: US20130142873A1
Автор: ASSAF MAHMOUD S., Connolly Terrence Joseph, JAMES ANGELA JOUBERT, KLOPFER KEVIN JOSEPH, Leong William Wei-Hwa, MENON Anil, MIKLOS Amanda Nicole
Принадлежит: SIGNAL PHARMACEUTICALS, LLC

Provided herein are compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, solid forms, isotopologues and metabolites thereof, and methods of their use for the treatment of a disease, disorder, or condition. 1. A pharmaceutical composition comprising an effective amount of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3 ,4-dihydropyrazino[2 ,3-b]pyrazin-2(1H)-one , or a pharmaceutically acceptable salt , isotopologue , metabolite or solid form thereof , stearic acid and lactose monohydrate.2. The pharmaceutical composition of claim 1 , comprising about 0.1-5% by weight of stearic acid.3. The pharmaceutical composition of claim 2 , comprising about 0.4% by weight of stearic acid.4. The pharmaceutical composition of claim 1 , comprising about 40-60% by weight of lactose monohydrate.5. The pharmaceutical composition of claim 4 , comprising about 49.2% by weight of lactose monohydrate.6. The pharmaceutical composition of claim 1 , further comprising microcrystalline cellulose.7. The pharmaceutical composition of claim 6 , wherein the microcrystalline cellulose is AVICEL PH 102®.8. The pharmaceutical composition of claim 7 , comprising about 20-40% by weight of AVICEL PH 102®.9. The pharmaceutical composition of claim 8 , comprising about 31% by weight of AVICEL PH 102®.10. The pharmaceutical composition of claim 1 , further comprising a disintegrant.11. The pharmaceutical composition of claim 10 , wherein the disintegrant is croscarmellose sodium.12. The pharmaceutical composition of claim 10 , wherein the disintegrant is AC-DI-SOL®.13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition comprises from about 1-5% by weight of AC-DI-SOL®.14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises about 40-60% by weight of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3 ...

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Номер записи: 84
06-06-2013 дата публикации

SUBSTITUTED DIBENZONAPHTHYRIDINES, PHARMACEUTICAL USES THEREOF AND PROCESSES THERFOR

Номер: US20130143878A1
Автор: Cushman Mark S., Kiselev Evgeny A.
Принадлежит: PURDUE RESEARCH FOUNDATION

The invention described herein pertains to substituted dibenzonaphthyridine compounds, pharmaceutical compositions, and formulations comprising the dibenzonaphthyridine compounds, their synthesis, and methods for their use in the treatment and/or prevention of cancer. 2. The compound of wherein Ris selected from the group consisting of hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted alkenyl claim 1 , optionally substituted alkynyl claim 1 , optionally substituted cycloalkyl claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , optionally substituted arylalkyl claim 1 , optionally substituted heteroarylalkyl claim 1 , and optionally substituted acyl.3. The compound of wherein Ris (CH)—Z claim 1 , where n is an integer from 1-6 claim 1 , and Zis selected from halo claim 1 , hydroxy claim 1 , alkoxy claim 1 , cycloalkoxy claim 1 , haloalkoxy claim 1 , halocycloalkoxy claim 1 , optionally substituted aryloxy claim 1 , optionally substituted heteroaryloxy claim 1 , acyloxy claim 1 , amino claim 1 , alkyl and dialkylamino claim 1 , trialkylammonium claim 1 , hydroxyalkylamino claim 1 , hydroxyalkylaminoalkylamino claim 1 , acylamino claim 1 , hydroxylamino claim 1 , alkoxylamino claim 1 , acyloxylamino claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , halocycloalkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , acyl claim 1 , cyano claim 1 , nitro claim 1 , azido claim 1 , thio claim 1 , alkylsulfonyl claim 1 , carboxylic acid and derivatives thereof claim 1 , sulfonic acid and derivatives thereof claim 1 , and phosphonic acid and derivatives thereof.4. The compound of wherein Zis dimethylamino.6. The compound of wherein n is 2 claim 3 , 3 claim 3 , or 4.78-. (canceled)9. The compound of wherein Ris substituted Calkyl.1011-. (canceled)12. The compound of wherein Ris hydrogen; or Rand the attached nitrogen form an amine prodrug.1315-. (canceled)16. The compound of wherein Rrepresents four substituents ...

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Номер записи: 85
06-06-2013 дата публикации

PHENOXYMETHYL HETEROCYCLIC COMPOUNDS

Номер: US20130143888A1
Автор: Chesworth Richard, Ripka Amy, Shapiro Gideon
Принадлежит: ENVIVO PHAMACEUTICALS, INC.

Phenoxymethyl compounds that inhibit at least one phosphodiesterase 10 are described as are pharmaceutical compositions containing such compounds an methods for treating various CNS disorders by administering such compounds to a patient in need thereof. 135.-. (canceled)36. A method for treating a central nervous system (CNS) disorder comprising administering to a human in need thereof a therapeutically effective amount of 4-(4-(imidazo[1 ,2-b]pyridazin-2-ylmethoxy)phenyl)-2 ,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one or a pharmaceutically acceptable salt thereof.37. The method of claim 36 , wherein the CNS disorder is one or more of Huntington's disease claim 36 , schizophrenia claim 36 , schizo-affective condition claim 36 , delusional disorder claim 36 , drug-induced psychosis claim 36 , panic disorder claim 36 , obsessive compulsive disorder claim 36 , post-traumatic stress disorder claim 36 , age-related cognitive decline claim 36 , attention deficit/hyperactivity disorder claim 36 , bipolar disorder claim 36 , personality disorder of the paranoid type claim 36 , personality disorder of the schizoid type claim 36 , dyskinesia claim 36 , choreiform condition claim 36 , psychosis associated with Parkinson's disease claim 36 , psychotic symptoms associated with Alzheimer's disease claim 36 , dystonic condition claim 36 , mood disorder claim 36 , and dementia.38. The method of claim 36 , wherein the CNS disorder is schizophrenia claim 36 , schizo-affective condition claim 36 , Huntington's disease claim 36 , bipolar disorder claim 36 , obsessive compulsive disorder claim 36 , dystonic condition claim 36 , or tardive dyskinesia.39. The method of claim 37 , wherein the dementia is multi-infarct dementia claim 37 , AIDS-related dementia claim 37 , or neurodegenerative dementia.40. The method of claim 36 , wherein the CNS disorder is schizophrenia or schizo-affective condition.41. The method of claim 36 , wherein the CNS disorder is Huntington's disease.42. The method ...

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Номер записи: 86
06-06-2013 дата публикации

Heterocycles As Potassium Channel Modulators

Номер: US20130143889A1
Автор: Amato George S., Atkinson Robert N., Barolli Maria Graciela, Christos Thomas Eugene, Suto Mark J., Wolf-Gouveia Lilli Ann
Принадлежит: ICAGEN INC.

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltage-dependent potassium channels. More particularly, the invention provides heterocycles, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, seizure, retinal degeneration, hearing and vision loss, Alzheimer's disease, age-10 related memory loss, learning deficiencies, anxiety, neuronal degeneration and motor neuron diseases, maintaining bladder control or treating urinary incontinence) and as neuroprotective agents (e.g., to prevent stroke and the like) by modulating potassium channels associated with the onset or recurrence of the indicated conditions. 16-. (canceled)910-. (canceled)12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Ris F or CF.13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein Ris cyclopropyl claim 12 , cyclobutyl claim 12 , cyclopentyl claim 12 , cyclohexyl claim 12 , 1-methylcyclopentyl claim 12 , 1-methylcyclopentylmethyl claim 12 , cyclohexylmethyl claim 12 , 4-trifluoromethyl-2-pyridyl claim 12 , 2 claim 12 ,2-dimethylpropyl or 3-methyl-1-butyl.14. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein Ris CF(CH)CCH— claim 12 , CF(CH)C— claim 12 , 3 claim 12 ,4-difluorophenyl or 1-methyl-cyclopentylmethyl.1537-. (canceled)38. A pharmaceutical composition comprising a compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , and a pharmaceutically acceptable excipient.39. A method of modulating activity of a potassium ion channel in a subject claim 7 , said method comprising:{'claim-ref': {'@idref': 'CLM-00007', ' ...

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Номер записи: 87
06-06-2013 дата публикации

BICYCLIC COMPOUNDS AND THEIR USES AS DUAL C-SRC / JAK INHIBITORS

Номер: US20130143895A1
Автор: Mc Allister Andrès, Murone Maximilien, Sengupta Saumitra, Shetty Shankar Jayaram
Принадлежит:

The present invention relates to substituted aromatic bicyclic compounds containing pyrimidine and pyridine rings of formula (I) having the structure as well as pharmaceutically acceptable salts thereof. The compounds of the present invention are useful as tyrosine kinase inhibitors, preferably SRC family kinases (SFKs) inhibitors, in particular as multi SFK/JAK. kinases inhibitors and even preferably as dual c-SRC/JAK kinases inhibitors, thereby inhibiting the STAT3 activation and therefore abnormal growth of particular cell types. Notably, the compounds of the present invention are useful for the treatment or inhibition of certain diseases that are the result of deregulation of STAT3. 114.-. (canceled)16. The method of claim 15 , wherein said disease is cancer claim 15 , an auto-immune disease claim 15 , a bone related disease or a haematological disease.17. The method of claim 16 , wherein said cancer is breast cancer claim 16 , head and neck cancer claim 16 , melanoma claim 16 , ovarian cancer claim 16 , lung cancer claim 16 , pancreatic cancer claim 16 , colon cancer claim 16 , uterine cancer claim 16 , gastric cancer claim 16 , renal cancer claim 16 , bladder cancer claim 16 , liver cancer or prostate cancer.18. The method of claim 16 , wherein said cancer is multiple myeloma claim 16 , a leukaemia claim 16 , a myeloproliferative neoplasm or a lymphoma.19. The method of claim 15 , wherein said administration is oral claim 15 , transdermal or parenteral.24. The method of claim 15 , wherein the compound of formula (I) is selected from the group consisting of:N-(4-Methyl-3-{2-[4-(4-methyl-piperazine-1-carbonyl)-phenylamino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-phenyl)-3-trifluoromethyl-benzamide;N-(4-Methyl-3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-phenyl)-3-trifluoromethyl-benzamide;5-{6-[2-Methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-ylamino}-pyridine- ...

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Номер записи: 88
06-06-2013 дата публикации

Process for preparing substituted 5-fluoro-1H-pyrazolopyridines

Номер: US20130143900A1
Автор: FEY Peter
Принадлежит: Bayer Intellectual Property GmbH

The present application relates to a novel and efficient process for preparing novel substituted 5-fluoro-1H-pyrazolopyridines of the formula (VI) 9. The compound of claim 8 , wherein the x-ray diffractogram of the compound exhibits peak maxima of the 2 theta angle at 5.9 claim 8 , 6.9 claim 8 , 22.7.10. The compound of claim 9 , wherein the x-ray diffractogram of the compound exhibits peak maxima of the 2 theta angle at 5.9 claim 9 , 6.9 claim 9 , 16.2 claim 9 , 16.5 claim 9 , 24.1 claim 9 , 22.7 claim 9 , 24.7.11. The compound of claim 8 , wherein the IR spectrum of the compound exhibits band maxima at 1707 claim 8 , 1633 claim 8 , 1475 cm.12. The compound of claim 11 , wherein the IR spectrum of the compound exhibits band maxima at 1707 claim 11 , 1633 claim 11 , 1566 claim 11 , 1475 claim 11 , 1255 claim 11 , 1223 cm.13. A process for preparing the compound of claim 8 , comprising:stiffing a solution of compounds of formula (I), wherein the compounds of formula (I) are present in one or more polymorphs or as a solvate in an inert solvent, at a temperature of 20° C.-120° C., andisolating the compound of formula (I) in the form of crystalline polymorph I from the solution.14. A pharmaceutical composition comprising a compound of and no greater proportion of any other form of the compound of the formula (I).15. A pharmaceutical composition comprising a compound of in more than 90 percent by weight based on the total amount any other form of the compound of the formula (I) present.16. A method for treatment of cardiovascular disorders by administering an effective amount of the compound of to a patient in need thereof.18. The crystalline substance compound of claim 17 , wherein the x-ray diffractogram of the compound exhibits peak maxima of the 2 theta angle at 18.8 claim 17 , 20.3 claim 17 , 21.7.19. The crystalline substance compound of claim 18 , wherein the x-ray diffractogram of the compound exhibits peak maxima of the 2 theta angle at 12.0 claim 18 , 16.6 ...

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Номер записи: 89
06-06-2013 дата публикации

PYRAZOLOQUINOLINE DERIVATIVES

Номер: US20130143907A1
Автор: Hagiwara Koji, Ishihara Yuki, Norimine Yoshihiko, Sato Nobuaki, Suzuki Yuichi, Takeda Kunitoshi
Принадлежит: Eisai R&D Management Co., Ltd.

A compound and/or pharmacologically acceptable salt thereof represented by the formula (I) has PDE9 inhibitory action, so that the intracerebral cGMP concentration is anticipated to be elevated. The PDE9 inhibitory action and the increase in cGMP lead to the improvement of learning and memory behaviors, and the compound (I) has applicability as a therapeutic agent for cognitive dysfunctions in Alzheimer's disease. 2. The compound and/or pharmacologically acceptable salt thereof according to claim 1 , wherein{'sup': '2', 'Ris an aromatic ring group selected from the group consisting of a phenyl group, a 3-pyridinyl group, a 4-pyridinyl group, and a 5-pyrimidinyl group, where the two atoms on the aromatic ring which are adjacent to the carbon atom attached to the pyrazolo[4,3-c]quinoline ring each independently has a substituent selected from Group A2, and the other atoms on the aromatic ring independently optionally have a substituent selected from Group B2;'}{'sup': '5', 'Ris a 4-oxepanyl group, a 1,4-dioxepan-6-yl group, a 3,4,5,6-tetrahydro-2H-3-pyranyl group, a 3,4,5,6-tetrahydro-2H-4-pyranyl group, or a 3-tetrahydrofuranyl group;'}Group A2 consists of a chlorine atom, and a methyl group optionally having 1 to 2 fluorine atoms, an ethyl group, a methoxy group, and an ethoxy group; andGroup B2 consists of a fluorine atom, a chlorine atom, a cyano group, a methyl group optionally having 1 to 3 fluorine atoms, an ethyl group, a methoxymethyl group, a methoxy group optionally having 1 to 3 fluorine atoms, an ethoxy group, an isopropyloxy group, and a 3,4,5,6-tetrahydro-2H-4-pyranyl group.3. The compound and/or pharmacologically acceptable salt thereof according to claim 2 , wherein Ris a fluorine atom.4. The compound and/or pharmacologically acceptable salt thereof according to claim 1 , wherein{'sup': '3', 'Ris a hydrogen atom; and'}{'sup': '5', 'Ris a tetrahydropyranyl group, or a tetrahydrofuranyl group optionally having a methoxy group.'}5. The compound and/or ...

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Номер записи: 90
06-06-2013 дата публикации

TRIAZOLOPYRIDINES AS TYK2 INHIBITORS

Номер: US20130143915A1
Автор: Ellard Katie, Ramsden Nigel
Принадлежит: CELLZOME LIMITED

The present invention relates to compounds of Formula (I), wherein Rto Rhave the meaning as cited in the description and the claims. Said compounds are useful as TYK2 inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immuno logically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds as well as their use as medicaments. 2. A compound of claim 1 , wherein{'sup': 2', '3', '8', '8a', '8a', '8, '(iii) when Ris F; Ris C(O)N(RR); Ris H then Ris other than 2-phenylethyl and 2-phenoxyethyl;'}{'sup': 2', '3', '8', '8, '(iv) when Ris F; Ris C(O)Rthen Ris other than piperidin-1-yl; and'}{'sup': 2', '3, 'sub': 3', '3, '(v) when Ris OCHthen Ris other than OCH.'}3. A compound of claim 1 , wherein Ris F; Cl; CF; OCH; or CH.4. A compound of claim 1 , wherein Ris F; or Cl.5. A compound of claim 1 , wherein Ris Cl.6. A compound of claim 1 , wherein Ris unsubstituted Calkyl; OR; Cl; S(O)R; N(RR); or N(R)S(O)R.7. A compound of claim 1 , wherein Ris S(O)R; or N(R)S(O)R.8. A compound of claim 1 , wherein Ris N(R)S(O)R.9. A compound of claim 1 , wherein Ris unsubstituted Ccycloalkyl.10. A compound of claim 1 , wherein Ris C(O)R.11. A compound of claim 1 , wherein Ris unsubstituted Ccycloalkyl.12. A compound of selected from the group consisting ofN-(5-(2,4-dichlorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(2-fluoro-4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(4-methoxy-2-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(2-chloro-4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(4-amino-2-chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(2-chloro-4-(methylsulfonamido)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;N-(5-(4-amino-2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl) ...

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Номер записи: 91
06-06-2013 дата публикации

NOVEL PRODUCTION METHOD FOR ISOQUINOLINE DERIVATIVES AND SALTS THEREOF

Номер: US20130144054A1
Автор: GOMI Noriaki, Ohgiya Tadaaki, Shibuya Kimiyuki
Принадлежит:

The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base. 2. The method according to claim 1 , wherein m and n in formulae (I) claim 1 , (II) claim 1 , and (III) are each 0.3. The method according to claim 1 , wherein Rin formulae (I) claim 1 , (II) claim 1 , and (III) is a methyl group.4. The method according to claim 1 , wherein the solvent is at least one solvent selected from the group consisting of N claim 1 ,N-dimethylformamide claim 1 , dimethylsulfoxide claim 1 , N-methylpyrrolidone claim 1 , N claim 1 ,N-dimethylpropyleneurea claim 1 , and acetonitrile.5. The method according to claim 1 , wherein the solvent is acetonitrile.6. The method according to claim 1 , wherein an amount of the solvent is 1 to 40 times an amount of a compound of formula (III).7. The method according to claim 1 , wherein the base is a tertiary amine.9. The method according to claim 8 , wherein the phosphine reagent is triphenylphosphine and the azo reagent is diisopropyl azodicarboxylate.11. The method according to claim 10 , wherein the phosphine reagent is triphenylphosphine and the azo reagent is diisopropyl azodicarboxylate.12. The method ...

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Номер записи: 92
13-06-2013 дата публикации

Inhibitors of PDE10

Номер: US20130150371A1
Автор: Chaturvedula Prasad V., Kimura S. Roy
Принадлежит:

PDE10 inhibitors having the general formula (I) 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl.3. A compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein R-Rare hydrogen.9. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.10. A method of treating a disorder selected from schizophrenia; positive claim 1 , negative claim 1 , and/or cognitive symptoms associated with schizophrenia; delusional disorder; substance-induced psychotic disorder; panic disorder; obsessive-compulsive disorder; acute stress disorder; generalized anxiety disorders; drug addiction; Parkinson's disease; Huntington's disease; restless leg syndrome; Alzheimer's disease; multi-infarct dementia; depression; bipolar disorders; psychosis claim 1 , and attention-deficit/hyperactivity disorder; in a patient claim 1 , comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.11. The method of wherein the disorder is schizophrenia. This application claims the benefit of U.S. Provisional Application Ser. No. 61/499,360 filed Jun. 21, 2011.The present disclosure is generally directed to compounds which inhibitPDE10, compositions comprising such compounds, and methods for inhibiting the function of the PDE10.Phosphodiesterases (PDEs) are intracellular enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to adenosine monophosphate (AMP) and guanosine monophosphate (GMP), respectively. cAMP and cGMP serve as secondary messengers in several cellular pathways. For example, cAMP and cGMP control activity of cAMP and cGMP-dependent kinases, as well as other proteins with cyclic nucleotide response elements, which in turn controls levels of phosphorylation of proteins that are involved in ...

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Номер записи: 93
13-06-2013 дата публикации

PYRIMIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF RESPIRATORY DISEASES SUCH AS COPD

Номер: US20130150380A1
Автор: Edwards Christine, Finch Harry, Kulagowski Janusz
Принадлежит: CHIESI FARMACEUTICI S.p.A.

Compounds of formula (I) are inhibitors of neutrophil elastase, wherein A is C—Ror N; —X-X— is CR═N— or —NR—CO—; and R-R, R, Rand Rare as defined in the claims. 2. A compound as claimed in wherein Ris hydrogen or 2-methanesulphonyl.3. A compound as claimed in claim 1 , wherein Ris hydrogen and Ris 3-trifluoromethyl claim 1 , 3-chloro or 3-bromo.5. A compound as claimed in claim 1 , wherein —X-X— is —NR—CO— and Ris methyl;6. A compound as claimed in claim 1 , in the form of a pharmaceutically acceptable salt.7. (canceled)8. A pharmaceutical composition comprising a compound as claimed in and a pharmaceutically acceptable carrier or excipient.9. A pharmaceutical composition as claimed in which is adapted for oral administration or administration by the pulmonary route.10. (canceled)11. A method of treatment of a disease or condition in which HNE is implicated claim 1 , comprising administering to a subject suffering such disease an effective amount of a compound as claimed in .12. A method of treatment according to claim 11 , wherein the disease or condition is chronic obstructive pulmonary disease (COPD) claim 11 , chronic bronchitis claim 11 , lung fibrosis claim 11 , pneumonia claim 11 , acute respiratory distress syndrome (ARDS) claim 11 , pulmonary emphysema claim 11 , smoking-induced emphysema or cystic fibrosis.13. A method of treatment according to claim 11 , wherein the disease or condition is asthma claim 11 , rhinitis claim 11 , psoriasis claim 11 , atopic dermatitis claim 11 , non-atopic dermatitis claim 11 , Crohn's disease claim 11 , ulcerative colitis claim 11 , or irritable bowel disease. This invention relates to heterocyclic compounds, which are pyrimidine derivatives having human neutrophil elastase inhibitory properties, and their use in therapy.Human neutrophil elastase (HNE) is a 32 kDa serine proteinase found in the azurophilic granules of neutrophils. It has a role in the degradation of a wide range of extracellular matrix proteins, including ...

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Номер записи: 94
13-06-2013 дата публикации

Indole Derivatives as CRTH2 Receptor Antagonists

Номер: US20130150398A1
Автор: Berthelette Carl, BOYD Michael, Colucci John, Methot Joey L., Villeneuve Karine
Принадлежит:

Compound of formula I are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-mediated diseases such as asthma. 216.-. (canceled)17. A method of treating a prostaglandin mediated disease comprising administering a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof to a mammalian patient in need thereof. This application claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Application No. 61/154,968, filed Feb. 24, 2009.Prostanglandin D(PGD) is a cyclooxygenase metabolite of arachidonic acid. It is released from mast and TH2 cells in response to an immunological challenge, and has been implicated in playing a role in different physiological events such as sleep and allergic responses.Receptors for PGDinclude the “DP” receptor, the chemoattractant receptor-homologous molecule expressed on TH2 cells (“CRTH2”), and the “FP” receptor. These receptors are G-protein coupled receptors activated by PGD. The CRTH2 receptor and its expression on different cells including human T-helper cells, basophils, and eosinophils are described in Abe, et al., 227:71-77, 1999, Nagata, et al., 459:195-199, 1999, and Nagata, et al., 162:1278-1286, 1999, describe CRTH2 receptor. Hirai, et al., 193:255-261, 2001, indicates that CRTH2 is a receptor for PGD.WO2007019675 discloses CRTH2 antagonists of the formula:The present invention provides novel compounds which are CRTH2 receptor antagonists. Compounds of the present invention are useful for the treatment of various prostaglandin-mediated diseases and disorders; accordingly the present invention provides a method for the treatment of prostaglandin-mediated diseases using the novel compounds described herein, as well as pharmaceutical compositions containing them.The present invention relates to compounds of formula I:and pharmaceutically acceptable salts thereof, wherein:represents eitherYis selected from optionally substituted aryl ...

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Номер записи: 95
13-06-2013 дата публикации

SALTS, PRODRUGS AND POLYMORPHS OF FAB I INHIBITORS

Номер: US20130150400A1
Автор: Pauls Henry, Ramnauth Jailall
Принадлежит: Affinium Pharmaceuticals, Inc.

In part, the present invention is directed to antibacterial compounds and salts thereof. 2. The compound of claim 1 , wherein the compound is in a crystalline form.3. The compound of claim 1 , wherein n equals 1 claim 1 , m equals 1 and X is HSOAr.4. The compound of claim 1 , wherein n equals 1 claim 1 , m equals 0 and X is HSOAr.5. The compound of claim 1 , wherein Ar is benzene or toluene.6. The compound of claim 1 , wherein the compound is an anhydrous p-toluenesulfonic salt.7. The salt according to with characteristic peaks in the powder X-ray diffraction pattern at values of 2θ as depicted in .8. The compound of claim 1 , wherein the compound is a mono claim 1 , di claim 1 , tri or fractional hydrate form of a p-toluenesulfonic salt.9. The salt of claim 8 , wherein the monohydrate form has characteristic peaks in the powder X-ray diffraction pattern at values of 20 substantially the same as depicted in .10. The compound of claim 1 , wherein the compound is a hydrochloric acid salt.11. The salt of claim 10 , wherein said salt has a powder X-ray diffraction pattern substantially that same as that depicted in .12. The compound of claim 1 , wherein the compound is a methane sulfonate salt.13. The salt of claim 12 , wherein said salt has a powder X-ray diffraction pattern substantially that same as that depicted in .14. The compound of claim 1 , wherein the compound is a benzenesulfonic salt.15. The salt according to claim 14 , wherein said salt has a powder X-ray diffraction pattern substantially that same as that depicted in .16. The salt according to claim 15 , wherein said salt has a powder X-ray diffraction pattern substantially that same as that depicted in .17. The compound of claim 1 , wherein the compound is a sulfate salt.18. The salt according to claim 17 , wherein said salt has a powder X-ray diffraction pattern substantially that same as that depicted in .19. A compound selected from the group consisting of:(E)-N-methyl-N-((3-methylbenzofuran-2-yl) ...

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Номер записи: 96
13-06-2013 дата публикации

PHOSPHINATE RUTHENIUM COMPLEXES

Номер: US20130150572A1
Автор: Alexandre Francois-Rene, Bonnaterre Florence Marie-Emilie, Parsy Christophe Claude, Surleraux Dominique
Принадлежит: IDENIX PHARMACEUTICALS, INC.

Provided herein are ruthenium complexes of Formula I, and processes of preparation thereof. Also provided are methods of their use as a metathesis catalyst. 5. The method of claim 1 , wherein L is a heterocyclic carbene or phosphine claim 1 ,wherein the heterocyclic carbene is optionally substituted with one or more substituents.7. The method of claim 6 , wherein Ror Ris hydrogen or methyl.8. The method of claim 6 , wherein Ror Ris hydrogen or methyl.9. The method of claim 6 , wherein Ris Caryl.10. The method of claim 6 , wherein Ris Caryl claim 6 , substituted with one or more Calkyl.11. The method of claim 10 , wherein Ris 2-methylphenyl claim 10 , 2 claim 10 ,4 claim 10 ,6-trimethylphenyl claim 10 , or 2 claim 10 ,6-di(isopropyl)phenyl.12. The method of claim 6 , wherein Ris Caryl.13. The method of claim 6 , wherein Ris Caryl claim 6 , substituted with one or more Calkyl.14. The method of claim 6 , wherein Ris 2-methylphenyl claim 6 , 2 claim 6 ,4 claim 6 ,6-trimethylphenyl claim 6 , or 2 claim 6 ,6-di(isopropyl)phenyl.16. The method of claim 5 , wherein the phosphine is PRRR claim 5 , wherein R claim 5 , R claim 5 , and Rare each independently Calkyl or Caryl claim 5 , each optionally substituted with one or more substituents.17. The method of claim 16 , wherein Ris phenyl or cyclohexyl.18. The method of claim 16 , wherein Ris phenyl or cyclohexyl.19. The method of claim 16 , wherein Ris phenyl or cyclohexyl.20. The method of claim 16 , wherein the phosphine is triphenylphosphine or tricyclohexylphosphine.21. The method of claim 1 , wherein Xis halide claim 1 , —C(O)R claim 1 , or —OC(O)R claim 1 , wherein Ris alkyl claim 1 , optionally substituted with one or more halides.22. The method of claim 21 , wherein Xis chloride.23. The method of claim 1 , wherein Xis halide claim 1 , —C(O)R claim 1 , or —OC(O)R claim 1 , wherein Ris alkyl claim 1 , optionally substituted with one or more halides.24. The method of claim 1 , wherein Xis chloride.25. The method of claim ...

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Номер записи: 97
13-06-2013 дата публикации

5-ANILINOIMIDAZOPYRIDINES AND METHODS OF USE

Номер: US20130150584A1
Автор: Heald Robert, Hewitt Joanne Frances Mary, Lee Wendy, PRICE Stephen, ZAK Mark E.
Принадлежит: Genentech, Inc.

The invention relates to a method of inhibiting abnormal cell growth or treating a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of an imidazopyridine of formula I with anti-hyperproliferative activity. 2. A compound of where the compound is the free base. This application is a continuation of U.S. Ser. No. 13/586,147, filed Aug. 15, 2012 which is a continuation of U.S. Ser. No. 13/041,735, filed Mar. 7, 2011 which is a divisional application of U.S. Pat. No. 7,923,456, issued Apr. 12, 2011, which claims the benefit of priority to international application number PCT/US2008/087482 and to U.S. provisional Application Ser. No. 61/015,129, filed 19 Dec. 2007, and to U.S. provisional Application Ser. No. 61/054,014, filed 16 May 2008, the disclosures of all are incorporated herein by reference in their entirety.The invention relates to imidazopyridines with anti-cancer activity and more specifically to imidazopyridines which inhibit MEK kinase activity. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.In the quest to understand how Ras transmits extracellular growth signals, the MAP (mitogen-activated protein) kinase (MAPK) pathway has emerged as the crucial route between membrane-bound Ras and the nucleus. The MAPK pathway encompasses a cascade of phosphorylation events involving three key kinases, namely Raf, MEK (MAP kinase kinase) and ERK (MAP kinase). Active GTP-bound Ras results in the activation and indirect phosphorylation of Raf kinase. Raf then phosphorylates MEK1 and 2 on two serine residues (S218 and 5222 for MEK1 and S222 and 5226 for MEK2) (Ahn et al., 2001, 332, 417-431). Activated MEK then phosphorylates its only known substrates, the MAP kinases, ERK1 and 2. ERK phosphorylation by MEK occurs on Y204 and T202 for ERK1 and Y185 and T183 for ERK2 (Ahn et al., ...

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Номер записи: 98
20-06-2013 дата публикации

RESPIRATORY FORMULATIONS AND COMPOUNDS FOR USE THEREIN

Номер: US20130156826A1
Автор: Joly Kevin, Murray Peter John, Onions Stuart Thomas, Williams Jonathan Gareth
Принадлежит: RESPIVERT LIMITED

The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I). 220-. (canceled)21. A formulation according to claim 1 , wherein the MMAD of the particles of the population is in the range 5 to 10 μm.22. A formulation according to claim 1 , wherein 50% of the particles of the population by number have a particle size within the specified range.23. (canceled)24. A formulation according to claim 1 , wherein the formulation further comprises an excipient or carrier.25. A formulation according to claim 24 , wherein the excipient is lactose.26. A formulation according to claim 24 , wherein the MMAD of the excipient is in the range 5 to 75 μm.27. A formulation according to claim 26 , wherein 50 claim 26 , 60 claim 26 , 70 claim 26 , 80 or 90% of the excipient has a mean particle size within the range.28. A formulation according to claim 1 , wherein the formulation is a dry powder formulation.29. (canceled)30. A formulation according to claim 1 , wherein the formulation is an aerosol formulation.31. A formulation according to claim 30 , wherein the formulation comprises a carrier which is a liquefied propellant gas.3260-. (canceled)62. A compound of formula (I) according to wherein Z represents —N═CR—.63. A compound of formula (I) according to wherein Z represents NH.64. A compound of formula (I) according to wherein Z represents O.65. A compound of formula (I) according to wherein J represents phenyl substituted by Rand R.66. A compound of formula (I) according to wherein J represents pyridinyl substituted by Rand R.67 ...

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Номер записи: 99
20-06-2013 дата публикации

Sodium alginate crosslinked slow-release moxifloxacin microsphere, the preparation method and the use thereof, and target vascular occlusive agent of the microsphere

Номер: US20130156827A1
Автор: Hong Hong, Xinjian Li
Принадлежит: BEIJING SHENGYIYAO TECHNOLOGY & DEVELOPMENT Co Ltd

A sodium alginate crosslinked slow-released moxifloxacin microsphere, the preparation method of the microsphere, a vascular target embolus containing the microsphere and the use of the microsphere in preparing the vascular target embolus. The microsphere contains moxifloxacin, a drug carrier, a adsorbent, a reinforcing agent and a solidifying agent, wherein the drug carrier is sodium alginate, the adsorbent is albumin prepared from human plasma or bovine serum albumin, the reinforcing agent is gelatin or hyaluronic acid, and the solidifying agent is a divalent metal cation chosen from calcium salt or barium salt.

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Номер записи: 100