RU2593500C2 - Новые модуляторы кортикальной дофаминергической и опосредованной nmda-рецептором глутаматергической нейротрансмиссии - Google Patents
Новые модуляторы кортикальной дофаминергической и опосредованной nmda-рецептором глутаматергической нейротрансмиссии Download PDFInfo
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- RU2593500C2 RU2593500C2 RU2013147917/04A RU2013147917A RU2593500C2 RU 2593500 C2 RU2593500 C2 RU 2593500C2 RU 2013147917/04 A RU2013147917/04 A RU 2013147917/04A RU 2013147917 A RU2013147917 A RU 2013147917A RU 2593500 C2 RU2593500 C2 RU 2593500C2
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- phenoxy
- ethyl
- methylsulfonyl
- fluoro
- amine
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Classifications
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- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
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- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Applications Claiming Priority (7)
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| US201161476810P | 2011-04-19 | 2011-04-19 | |
| US61/476,810 | 2011-04-19 | ||
| DKPA201170187 | 2011-04-19 | ||
| DKPA201170187 | 2011-04-19 | ||
| DKPA201170495 | 2011-09-06 | ||
| DKPA201170495 | 2011-09-06 | ||
| PCT/EP2012/056959 WO2012143337A1 (en) | 2011-04-19 | 2012-04-17 | Novel modulators of cortical dopaminergic- and nmda-receptor-mediated glutamatergic neurotransmission |
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| RU2013147917A RU2013147917A (ru) | 2015-05-27 |
| RU2593500C2 true RU2593500C2 (ru) | 2016-08-10 |
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| RU2013147917/04A RU2593500C2 (ru) | 2011-04-19 | 2012-04-17 | Новые модуляторы кортикальной дофаминергической и опосредованной nmda-рецептором глутаматергической нейротрансмиссии |
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| EP (1) | EP2699543B1 (enExample) |
| JP (1) | JP5876140B2 (enExample) |
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| JP6789681B2 (ja) * | 2016-06-10 | 2020-11-25 | スリーエム イノベイティブ プロパティズ カンパニー | グラフィックフィルム、ライセンスプレート、及びグラフィックフィルムの製造方法 |
| US12275694B2 (en) * | 2019-05-24 | 2025-04-15 | Irl 790 Ab | Pharmaceutically acceptable salts of [2-(3-fluoro-5-methane-sulfonylphenoxy)ethyl](propyl)amine and uses thereof |
| US20230147129A1 (en) | 2020-03-27 | 2023-05-11 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of synucleinopathies |
| JP2023548429A (ja) | 2020-11-10 | 2023-11-16 | インテグレイティブ・リサーチ・ラボラトリーズ・スウェーデン・アーベー | パーキンソン病、特にｌ－ｄｏｐａ誘発性ジスキネジアのための医薬品に対する感作の予防または軽減における使用のための［２－（３－フルオロ－５－メタンスルホニルフェノキシ）エチル］（プロピル）アミン（メスドペタム） |
| WO2024042540A1 (en) * | 2022-08-24 | 2024-02-29 | Alkem Laboratories Limited | Mesdopetam compositions |
| CA3268423A1 (en) | 2022-09-21 | 2024-03-28 | Assia Chemical Industries Ltd. | Solid state forms of mesdopetam and salts thereof |
| GB202312055D0 (en) | 2023-08-07 | 2023-09-20 | Ipsen Biopharm Ltd | Pharmaceutical compositions |
Citations (3)
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| RU2032669C1 (ru) * | 1987-08-07 | 1995-04-10 | Санофи | Способ получения аминофеноксипроизводных |
| WO2002000602A1 (en) * | 2000-06-30 | 2002-01-03 | Pfizer Products Inc. | Benzophenones and sulfones as inhibitors of glycine uptake |
| WO2007072041A1 (en) * | 2005-12-23 | 2007-06-28 | Astex Therapeutics Limited | Therapeutic compounds |
Family Cites Families (10)
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| JPS51123821A (en) | 1975-04-18 | 1976-10-28 | Nippon Kayaku Co Ltd | An algicide and protective agent |
| GB8823405D0 (en) * | 1988-10-05 | 1988-11-09 | Erba Carlo Spa | Aryloxy-arythio-heteraryloxy-heteroarylthio-alkenylene derivatives of amines |
| ES2169102T3 (es) * | 1994-10-14 | 2002-07-01 | Merck Patent Gmbh | (r)-(-)-2-(5-(4-fluorfenil)-3-piridilmetilaminometil)-cromano como agente activo sobre el sistema nervioso central. |
| GB0428235D0 (en) * | 2004-12-23 | 2005-01-26 | Glaxo Group Ltd | Novel compounds |
| JP2006193494A (ja) | 2005-01-17 | 2006-07-27 | Dainippon Ink & Chem Inc | ４級アンモニウム系化合物を有効成分とする心臓疾患治療剤 |
| WO2007063789A1 (ja) * | 2005-11-29 | 2007-06-07 | Kissei Pharmaceutical Co., Ltd. | 新規なカテコール誘導体、それを含有する医薬組成物およびそれらの用途 |
| AU2007218086A1 (en) * | 2006-02-15 | 2007-08-30 | M's Science Corporation | Piperazine derivatives |
| WO2009133110A1 (en) | 2008-04-29 | 2009-11-05 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Modulators of dopamine neurotransmission |
| JP2011519839A (ja) | 2008-04-29 | 2011-07-14 | エヌエスエイビー、フィリアル アヴ ノイロサーチ スウェーデン エービー、スヴェーリエ | ドーパミン神経伝達のモジュレーター |
| MX2010011724A (es) | 2008-04-29 | 2010-11-30 | Nsab Af Neurosearch Sweden Ab | Moduladores de neurotransmision de dopamina. |
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2012
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- 2012-04-17 PL PL12714704.9T patent/PL2699543T3/pl unknown
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- 2012-04-17 AU AU2012244867A patent/AU2012244867C1/en active Active
- 2012-04-17 DK DK12714704.9T patent/DK2699543T3/en active
- 2012-04-17 ES ES12714704.9T patent/ES2566634T3/es active Active
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- 2012-04-17 WO PCT/EP2012/056959 patent/WO2012143337A1/en not_active Ceased
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- 2012-04-17 CA CA2832874A patent/CA2832874C/en active Active
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2015
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2032669C1 (ru) * | 1987-08-07 | 1995-04-10 | Санофи | Способ получения аминофеноксипроизводных |
| WO2002000602A1 (en) * | 2000-06-30 | 2002-01-03 | Pfizer Products Inc. | Benzophenones and sulfones as inhibitors of glycine uptake |
| WO2007072041A1 (en) * | 2005-12-23 | 2007-06-28 | Astex Therapeutics Limited | Therapeutic compounds |
Non-Patent Citations (1)
| Title |
|---|
| RAUBO P. et al., Aminoalkyl phenyl sulfones - a novel series of 5-HT7 receptor ligands, Bioorganic & Medicinal Chemistry Letters, 2006, v. 16, no. 5, p. 1255-1258. * |
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| AU2012244867B2 (en) | 2016-07-28 |
| JP5876140B2 (ja) | 2016-03-02 |
| ZA201307227B (en) | 2014-12-23 |
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| IL228705A0 (en) | 2013-12-31 |
| AU2012244867A1 (en) | 2013-10-17 |
| ES2566634T3 (es) | 2016-04-14 |
| IL228705A (en) | 2016-11-30 |
| US20140128360A1 (en) | 2014-05-08 |
| SG193992A1 (en) | 2013-11-29 |
| CA2832874C (en) | 2019-06-11 |
| US9120728B2 (en) | 2015-09-01 |
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| US9006227B2 (en) | 2015-04-14 |
| RU2013147917A (ru) | 2015-05-27 |
| JP2014518552A (ja) | 2014-07-31 |
| PL2699543T3 (pl) | 2016-10-31 |
| MX341847B (es) | 2016-09-05 |
| MX2013012025A (es) | 2014-06-23 |
| WO2012143337A1 (en) | 2012-10-26 |
| US20150148426A1 (en) | 2015-05-28 |
| CN103476746B (zh) | 2015-10-14 |
| KR20140024901A (ko) | 2014-03-03 |
| KR101964406B1 (ko) | 2019-04-01 |
| HK1192877A1 (zh) | 2014-09-05 |
| DK2699543T3 (en) | 2016-03-29 |
| CN103476746A (zh) | 2013-12-25 |
| AU2012244867C1 (en) | 2017-01-19 |
| EP2699543A1 (en) | 2014-02-26 |
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