RU2440997C2 - Производные циннамоил-пиперазина и их применение в качестве антагонистов par-1 - Google Patents
Производные циннамоил-пиперазина и их применение в качестве антагонистов par-1 Download PDFInfo
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- RU2440997C2 RU2440997C2 RU2008152247/04A RU2008152247A RU2440997C2 RU 2440997 C2 RU2440997 C2 RU 2440997C2 RU 2008152247/04 A RU2008152247/04 A RU 2008152247/04A RU 2008152247 A RU2008152247 A RU 2008152247A RU 2440997 C2 RU2440997 C2 RU 2440997C2
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- RU
- Russia
- Prior art keywords
- piperazin
- propenone
- chlorophenyl
- difluorophenyl
- compound according
- Prior art date
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
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- Orthopedic Medicine & Surgery (AREA)
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- Pulmonology (AREA)
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| FR0605419A FR2902426B1 (fr) | 2006-06-19 | 2006-06-19 | Derives de cinnamoyl-piperazine |
| FR0605419 | 2006-06-19 |
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| RU2008152247A RU2008152247A (ru) | 2010-07-27 |
| RU2440997C2 true RU2440997C2 (ru) | 2012-01-27 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2662308C1 (ru) * | 2017-12-25 | 2018-07-25 | Феркат Адельзянович Халиуллин | Средство для лечения и профилактики тромбоза |
| RU2678309C1 (ru) * | 2013-12-16 | 2019-01-25 | Пьер Фабр Медикамент | Применение антагонистов активируемых протеазой рецепторов 1 (par-1) для профилактики и/или лечения функциональных патологических состояний в области таза и промежности |
| RU2762280C2 (ru) * | 2016-08-04 | 2021-12-17 | Метаболис | Новое лекарственное средство для лечения неалкогольного стеатогепатита и фиброза |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3143036B1 (en) | 2014-05-11 | 2023-08-02 | Tel Hashomer Medical Research Infrastructure and Services Ltd. | Par-1 based therapeutic conjugates and uses thereof |
| WO2016066789A1 (fr) * | 2014-10-31 | 2016-05-06 | Pierre Fabre Medicament | Utilisation d'antagonistes par-1 pour la prevention et/ou le traitement des pathologies fonctionnelles pelvi-perineales |
| CN104496922B (zh) * | 2015-01-13 | 2016-04-06 | 佛山市赛维斯医药科技有限公司 | 腈基苯二烯四氮唑类化合物、其制备方法和用途 |
| CN104496924B (zh) * | 2015-01-13 | 2016-04-13 | 佛山市赛维斯医药科技有限公司 | 卤苯二烯四氮唑类化合物、其制备方法和用途 |
| CN104529860B (zh) * | 2015-01-13 | 2016-06-01 | 佛山市赛维斯医药科技有限公司 | 一种含硝基苯和二烯氟代金刚烷结构的化合物及制备方法 |
| CN104496879A (zh) * | 2015-01-13 | 2015-04-08 | 佛山市赛维斯医药科技有限公司 | 一种含腈基苯和二烯氟代金刚烷结构的化合物和用途 |
| CN105949116A (zh) * | 2016-06-08 | 2016-09-21 | 青岛理工大学 | 酰基哌嗪类化合物及其制备方法和用途 |
| IL278311B2 (en) | 2018-05-02 | 2024-02-01 | Tel Hashomer Medical Res Infrastructure & Services Ltd | Preparations and methods for the treatment of glioblastoma |
| FR3090317B1 (fr) | 2018-12-19 | 2021-05-07 | Cvasthera | Utilisation d’un antagoniste de par-1 pour le traitement d’une maladie inflammatoire chronique intestinale |
| KR102791326B1 (ko) * | 2021-09-29 | 2025-04-04 | 주성수 | 피페론구민계 화합물을 유효성분으로 포함하는 혈관질환 예방 또는 치료용 약학적 조성물 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0209843A2 (en) * | 1985-07-16 | 1987-01-28 | Kanebo, Ltd. | Benzylpiperazine compound, preparation thereof, pharmaceutical composition, and use |
| RU2127732C1 (ru) * | 1992-06-25 | 1999-03-20 | Фармация и Апджон Актиеболаг | Эфиры бис-фенилпиперазинникотиновой кислоты, способ их получения (варианты), фармацевтическая композиция и способ лечения расстройств центральной нервной системы |
| WO2002076965A1 (en) * | 2001-03-23 | 2002-10-03 | John Matsoukas | Non peptide mimetics based on the active sequence s42fllr46 of the thrombin receptor for the treatment of thrombosis and cancer |
| WO2004037796A2 (en) * | 2002-10-25 | 2004-05-06 | Novartis Ag | 1-(4-benzyl-piperazin-1-yl)-3-phenyl-propenone derivatives |
| RU2005117383A (ru) * | 2002-11-07 | 2006-01-20 | Мерк энд Ко., Инк. (US) | Производные фенилаланина в качестве ингибиторов дипептидилпептидазы для лечения или профилактики диабета |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61106564A (ja) * | 1984-10-30 | 1986-05-24 | Terumo Corp | 不飽和脂肪酸アミド誘導体およびこれを含有する血小板凝集抑制剤 |
| US6207665B1 (en) * | 1997-06-12 | 2001-03-27 | Schering Aktiengesellschaft | Piperazine derivatives and their use as anti-inflammatory agents |
| CN1775762A (zh) * | 2005-12-06 | 2006-05-24 | 山东大学 | 川芎嗪酰基哌嗪衍生物、制备方法和药物组合物与应用 |
| FR2917622B1 (fr) * | 2007-06-19 | 2009-10-23 | Pierre Fabre Medicament Sa | Utilisation d'un antagoniste par1 dans le traitement de la fibrillation atriale. |
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2006
- 2006-06-19 FR FR0605419A patent/FR2902426B1/fr not_active Expired - Fee Related
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- 2007-06-19 MX MX2008016447A patent/MX2008016447A/es active IP Right Grant
- 2007-06-19 DE DE602007008572T patent/DE602007008572D1/de active Active
- 2007-06-19 AU AU2007263051A patent/AU2007263051B2/en not_active Ceased
- 2007-06-19 EP EP07786761A patent/EP2041104B1/en active Active
- 2007-06-19 CA CA2655527A patent/CA2655527C/en not_active Expired - Fee Related
- 2007-06-19 GE GEAP200711058A patent/GEP20115201B/en unknown
- 2007-06-19 BR BRPI0713132A patent/BRPI0713132B8/pt not_active IP Right Cessation
- 2007-06-19 UA UAA200900373A patent/UA96947C2/ru unknown
- 2007-06-19 US US12/305,584 patent/US8217046B2/en not_active Expired - Fee Related
- 2007-06-19 SA SA07280330A patent/SA07280330B1/ar unknown
- 2007-06-19 AT AT07786761T patent/ATE478059T1/de not_active IP Right Cessation
- 2007-06-19 PL PL07786761T patent/PL2041104T3/pl unknown
- 2007-06-19 PT PT07786761T patent/PT2041104E/pt unknown
- 2007-06-19 AR ARP070102685A patent/AR061520A1/es active IP Right Grant
- 2007-06-19 ES ES07786761T patent/ES2349324T3/es active Active
- 2007-06-19 NZ NZ573764A patent/NZ573764A/en not_active IP Right Cessation
- 2007-06-19 JP JP2009515860A patent/JP5356222B2/ja not_active Expired - Fee Related
- 2007-06-19 CN CN200780022674XA patent/CN101472907B/zh not_active Expired - Fee Related
- 2007-06-19 KR KR1020097000946A patent/KR101468752B1/ko not_active Expired - Fee Related
- 2007-06-19 WO PCT/EP2007/056086 patent/WO2007147824A1/en not_active Ceased
- 2007-06-19 RU RU2008152247/04A patent/RU2440997C2/ru active
- 2007-06-19 MY MYPI20085203A patent/MY144461A/en unknown
- 2007-06-20 TW TW096122073A patent/TWI404710B/zh not_active IP Right Cessation
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2008
- 2008-12-16 TN TNP2008000522A patent/TNSN08522A1/en unknown
- 2008-12-16 CR CR10509A patent/CR10509A/es unknown
- 2008-12-16 IL IL195972A patent/IL195972A/en active IP Right Grant
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2009
- 2009-01-09 MA MA31560A patent/MA30756B1/fr unknown
- 2009-01-13 EC EC2009009065A patent/ECSP099065A/es unknown
- 2009-01-14 ZA ZA2009/00303A patent/ZA200900303B/en unknown
- 2009-01-16 NO NO20090270A patent/NO341389B1/no not_active IP Right Cessation
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2012
- 2012-05-21 US US13/476,487 patent/US8513258B2/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0209843A2 (en) * | 1985-07-16 | 1987-01-28 | Kanebo, Ltd. | Benzylpiperazine compound, preparation thereof, pharmaceutical composition, and use |
| RU2127732C1 (ru) * | 1992-06-25 | 1999-03-20 | Фармация и Апджон Актиеболаг | Эфиры бис-фенилпиперазинникотиновой кислоты, способ их получения (варианты), фармацевтическая композиция и способ лечения расстройств центральной нервной системы |
| WO2002076965A1 (en) * | 2001-03-23 | 2002-10-03 | John Matsoukas | Non peptide mimetics based on the active sequence s42fllr46 of the thrombin receptor for the treatment of thrombosis and cancer |
| WO2004037796A2 (en) * | 2002-10-25 | 2004-05-06 | Novartis Ag | 1-(4-benzyl-piperazin-1-yl)-3-phenyl-propenone derivatives |
| RU2005115964A (ru) * | 2002-10-25 | 2006-01-27 | Новартис АГ (CH) | Производные 1-(4-бензилпиперазин-1-ил)-3-фенилпропенона |
| RU2005117383A (ru) * | 2002-11-07 | 2006-01-20 | Мерк энд Ко., Инк. (US) | Производные фенилаланина в качестве ингибиторов дипептидилпептидазы для лечения или профилактики диабета |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2678309C1 (ru) * | 2013-12-16 | 2019-01-25 | Пьер Фабр Медикамент | Применение антагонистов активируемых протеазой рецепторов 1 (par-1) для профилактики и/или лечения функциональных патологических состояний в области таза и промежности |
| RU2762280C2 (ru) * | 2016-08-04 | 2021-12-17 | Метаболис | Новое лекарственное средство для лечения неалкогольного стеатогепатита и фиброза |
| RU2662308C1 (ru) * | 2017-12-25 | 2018-07-25 | Феркат Адельзянович Халиуллин | Средство для лечения и профилактики тромбоза |
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