RU2353619C2 - Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции - Google Patents
Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции Download PDFInfo
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- RU2353619C2 RU2353619C2 RU2007124202/04A RU2007124202A RU2353619C2 RU 2353619 C2 RU2353619 C2 RU 2353619C2 RU 2007124202/04 A RU2007124202/04 A RU 2007124202/04A RU 2007124202 A RU2007124202 A RU 2007124202A RU 2353619 C2 RU2353619 C2 RU 2353619C2
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- Prior art keywords
- plasma
- hydrogen
- thrombin
- 6alkyl
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Classifications
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2007124202/04A RU2353619C2 (ru) | 2007-06-28 | 2007-06-28 | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
| JP2010514672A JP2010531353A (ja) | 2007-06-28 | 2008-06-27 | 新規抗凝血組成物、それらを基にした血栓症疾患治療のための医薬組成品、および血液希釈による凝固亢進障害改善のための血漿代用液 |
| US12/666,250 US8426433B2 (en) | 2007-06-28 | 2008-06-27 | Anticoagulant compounds, pharmaceutical compositions on their basis to treat thrombotic conditions, and plasma-substituting solution to correct hypercoagulation defects of hemodilution |
| EP08794029A EP2178839A2 (en) | 2007-06-28 | 2008-06-27 | New anticoagulant compounds, pharmaceutical compositions on their basis to treat thrombotic conditions, and plasma-substituting solution to correct hypercoagulation defects of hemodilution |
| CN200880104823.1A CN101848894B (zh) | 2007-06-28 | 2008-06-27 | 新型抗凝血剂化合物、以其为基础治疗血栓形成病况的药物组合物,和用来纠正血液稀释的高凝血缺陷的血浆代用液 |
| KR1020107002061A KR20100028122A (ko) | 2007-06-28 | 2008-06-27 | 신규한 항응고제 화합물, 혈전성 질환을 치료하기 위한 이러한 화합물을 기초로 한 약제 조성물, 및 혈액희석의 응고항진증을 치료하기 위한 혈장-대체 용액 |
| PCT/RU2008/000401 WO2009002229A2 (en) | 2007-06-28 | 2008-06-27 | New anticoagulant compounds, pharmaceutical compositions on their basis to treat thrombotic conditions, and plasma-substituting solution to correct hypercoagulation defects of hemodilution |
| AU2008269258A AU2008269258B2 (en) | 2007-06-28 | 2008-06-27 | New anticoagulant compounds, pharmaceutical compositions on their basis to treat thrombotic conditions, and plasma-substituting solution to correct hypercoagulation defects of hemodilution |
| UAA201000790A UA98969C2 (ru) | 2007-06-28 | 2008-06-27 | АНТИКОАГУЛЯНТНЫЕ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ ДЛЯ ЛЕЧЕНИЯ тромботических состояний И ПЛАЗМОЗАМЕЩАЮЩИЙ РАСТВОР ДЛЯ КОРРЕКЦИИ ГИПЕРКОАГУЛЯНТНЫХ НАРУШЕНИЙ ПРИ ГЕМОДИЛЮЦИИ |
| CA002692363A CA2692363A1 (en) | 2007-06-28 | 2008-06-27 | New anticoagulant compounds, pharmaceutical compositions comprising these compounds for treatment of thrombotic states, and plasma-substituting solutions to correct hypercoagulation defects of hemodilution |
| EA201000064A EA020915B1 (ru) | 2007-06-28 | 2008-06-27 | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2007124202/04A RU2353619C2 (ru) | 2007-06-28 | 2007-06-28 | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007124202A RU2007124202A (ru) | 2009-01-10 |
| RU2353619C2 true RU2353619C2 (ru) | 2009-04-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007124202/04A RU2353619C2 (ru) | 2007-06-28 | 2007-06-28 | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8426433B2 (enExample) |
| EP (1) | EP2178839A2 (enExample) |
| JP (1) | JP2010531353A (enExample) |
| KR (1) | KR20100028122A (enExample) |
| CN (1) | CN101848894B (enExample) |
| AU (1) | AU2008269258B2 (enExample) |
| CA (1) | CA2692363A1 (enExample) |
| EA (1) | EA020915B1 (enExample) |
| RU (1) | RU2353619C2 (enExample) |
| UA (1) | UA98969C2 (enExample) |
| WO (1) | WO2009002229A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2685261C1 (ru) * | 2018-04-05 | 2019-04-17 | Общество с ограниченной ответственностью "ФК ЛАБОРАТОРИЗ" | Вещество 4-амино-1-{ 2-[3-метил-5-(бензолсульфонилокси)фенокси] этил} -пиридиний хлорид, обладающее свойствами биологически активного агента, влияющими на естественно текущие процессы свертываемости крови млекопитающих, антикоагулянт на его основе и способ его получения путем химического синтеза |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2354647C2 (ru) * | 2007-06-28 | 2009-05-10 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией ингибиторов тромбина, и фармацевтические композиции на их основе |
| RU2353619C2 (ru) * | 2007-06-28 | 2009-04-27 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
| EA021562B1 (ru) * | 2012-08-15 | 2015-07-30 | Общество С Ограниченной Ответственностью "Гематологическая Корпорация" | Устройство мониторинга пространственного свертывания крови и ее компонентов |
| CN116444506A (zh) * | 2014-02-07 | 2023-07-18 | 艾克赛特赫拉制药有限责任公司 | 治疗化合物和组合物 |
| CN114080382B (zh) * | 2019-06-19 | 2024-05-24 | 株式会社Lg化学 | 制备吲哚或吲唑化合物的方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5510369A (en) * | 1994-07-22 | 1996-04-23 | Merck & Co., Inc. | Pyrrolidine thrombin inhibitors |
| US5792799A (en) * | 1996-10-10 | 1998-08-11 | Athena Neurosciences, Inc. | Parenteral delivery of MAO A inhibitors |
| RU2126388C1 (ru) * | 1993-03-03 | 1999-02-20 | Берингер Маннхайм ГмбХ | 4-аминопиридины и фармацевтическая композиция |
| RU2300385C1 (ru) * | 2005-12-27 | 2007-06-10 | Елена Ивановна Синауридзе | Раствор для коррекции первичных нарушений гемостаза плазмозамещающими растворами нового состава |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1245937B (enExample) * | 1964-09-09 | 1967-08-03 | ||
| US5089634A (en) * | 1984-08-20 | 1992-02-18 | Georgia Tech Research Corporation | Isocoumarins with cationic substituents |
| JPH0341065A (ja) * | 1989-07-06 | 1991-02-21 | Morishita Pharmaceut Co Ltd | アリールオキシアルキルイソチオウレア臭化水素酸塩類 |
| JP3084458B2 (ja) * | 1991-11-08 | 2000-09-04 | コニカ株式会社 | ハロゲン化銀写真感光材料 |
| IL109319A0 (en) * | 1993-04-27 | 1994-07-31 | Du Pont Merck Pharma | Amidino and guanidino substituted boronic acid compounds |
| DE4430757A1 (de) * | 1994-08-30 | 1996-03-07 | Boehringer Mannheim Gmbh | Neue 4-Aminopyridazine, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
| US5792769A (en) * | 1995-09-29 | 1998-08-11 | 3-Dimensional Pharmaceuticals, Inc. | Guanidino protease inhibitors |
| ATE341317T1 (de) * | 1996-03-29 | 2006-10-15 | Ortho Mcneil Pharm Inc | Amidinohydrazone als protease-inhibitoren |
| GB9613718D0 (en) * | 1996-06-29 | 1996-08-28 | Thrombosis Res Inst | Thrombin inhibitors |
| AU725403B2 (en) * | 1996-09-13 | 2000-10-12 | Merck & Co., Inc. | Thrombin inhibitors |
| US5886191A (en) * | 1997-08-18 | 1999-03-23 | Dupont Pharmaceuticals Company | Amidinoindoles, amidinoazoles, and analogs thereof |
| UA75093C2 (en) * | 2000-10-06 | 2006-03-15 | Dimensional Pharm Inc | Aminopyridinyl-,aminoguanidinyl-, and alkoxyguanidinesubstituted phenylsubstituted phenylacetamides as protease inhibitors |
| JP4896387B2 (ja) * | 2003-09-30 | 2012-03-14 | 武田薬品工業株式会社 | チアゾリン誘導体およびその用途 |
| AU2005229505B2 (en) * | 2004-03-02 | 2010-07-15 | F. Hoffmann-La Roche Ag | 4- (sulfanyl-pyrimidin-4-ylmethyl) -morpholine derivatives and related compounds as GABA receptor ligands for the treatment of anxiety, depression and epilepsy |
| CA2647597A1 (en) * | 2006-05-31 | 2007-12-06 | Abbott Laboratories | Thiazole compounds as cannabinoid receptor ligands and uses thereof |
| RU2353619C2 (ru) * | 2007-06-28 | 2009-04-27 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
| RU2354647C2 (ru) * | 2007-06-28 | 2009-05-10 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией ингибиторов тромбина, и фармацевтические композиции на их основе |
-
2007
- 2007-06-28 RU RU2007124202/04A patent/RU2353619C2/ru not_active IP Right Cessation
-
2008
- 2008-06-27 AU AU2008269258A patent/AU2008269258B2/en not_active Ceased
- 2008-06-27 EP EP08794029A patent/EP2178839A2/en not_active Withdrawn
- 2008-06-27 KR KR1020107002061A patent/KR20100028122A/ko not_active Abandoned
- 2008-06-27 US US12/666,250 patent/US8426433B2/en not_active Expired - Fee Related
- 2008-06-27 CA CA002692363A patent/CA2692363A1/en not_active Abandoned
- 2008-06-27 UA UAA201000790A patent/UA98969C2/ru unknown
- 2008-06-27 EA EA201000064A patent/EA020915B1/ru not_active IP Right Cessation
- 2008-06-27 JP JP2010514672A patent/JP2010531353A/ja active Pending
- 2008-06-27 WO PCT/RU2008/000401 patent/WO2009002229A2/en not_active Ceased
- 2008-06-27 CN CN200880104823.1A patent/CN101848894B/zh not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2126388C1 (ru) * | 1993-03-03 | 1999-02-20 | Берингер Маннхайм ГмбХ | 4-аминопиридины и фармацевтическая композиция |
| US5510369A (en) * | 1994-07-22 | 1996-04-23 | Merck & Co., Inc. | Pyrrolidine thrombin inhibitors |
| US5792799A (en) * | 1996-10-10 | 1998-08-11 | Athena Neurosciences, Inc. | Parenteral delivery of MAO A inhibitors |
| RU2300385C1 (ru) * | 2005-12-27 | 2007-06-10 | Елена Ивановна Синауридзе | Раствор для коррекции первичных нарушений гемостаза плазмозамещающими растворами нового состава |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2685261C1 (ru) * | 2018-04-05 | 2019-04-17 | Общество с ограниченной ответственностью "ФК ЛАБОРАТОРИЗ" | Вещество 4-амино-1-{ 2-[3-метил-5-(бензолсульфонилокси)фенокси] этил} -пиридиний хлорид, обладающее свойствами биологически активного агента, влияющими на естественно текущие процессы свертываемости крови млекопитающих, антикоагулянт на его основе и способ его получения путем химического синтеза |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2008269258B2 (en) | 2012-12-13 |
| JP2010531353A (ja) | 2010-09-24 |
| AU2008269258A1 (en) | 2008-12-31 |
| WO2009002229A3 (en) | 2009-03-12 |
| CN101848894B (zh) | 2014-08-20 |
| CA2692363A1 (en) | 2008-12-31 |
| EA020915B1 (ru) | 2015-02-27 |
| RU2007124202A (ru) | 2009-01-10 |
| CN101848894A (zh) | 2010-09-29 |
| UA98969C2 (ru) | 2012-07-10 |
| EA201000064A1 (ru) | 2010-06-30 |
| KR20100028122A (ko) | 2010-03-11 |
| EP2178839A2 (en) | 2010-04-28 |
| WO2009002229A2 (en) | 2008-12-31 |
| US20110003826A1 (en) | 2011-01-06 |
| US8426433B2 (en) | 2013-04-23 |
| AU2008269258A8 (en) | 2010-03-25 |
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