CA2810004C - Crystalline forms of a factor xa inhibitor - Google Patents
Crystalline forms of a factor xa inhibitor Download PDFInfo
- Publication number
- CA2810004C CA2810004C CA2810004A CA2810004A CA2810004C CA 2810004 C CA2810004 C CA 2810004C CA 2810004 A CA2810004 A CA 2810004A CA 2810004 A CA2810004 A CA 2810004A CA 2810004 C CA2810004 C CA 2810004C
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- 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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Landscapes
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- Pulmonology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37933910P | 2010-09-01 | 2010-09-01 | |
| US61/379,339 | 2010-09-01 | ||
| US201161454396P | 2011-03-18 | 2011-03-18 | |
| US61/454,396 | 2011-03-18 | ||
| PCT/US2011/050057 WO2012031017A1 (en) | 2010-09-01 | 2011-08-31 | CRYSTALLINE FORMS OF A FACTOR Xa INHIBITOR |
Publications (2)
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| CA2810004A1 CA2810004A1 (en) | 2012-03-08 |
| CA2810004C true CA2810004C (en) | 2019-09-10 |
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| CA2810004A Expired - Fee Related CA2810004C (en) | 2010-09-01 | 2011-08-31 | Crystalline forms of a factor xa inhibitor |
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| PT (1) | PT2611779T (enExample) |
| TW (1) | TW201221128A (enExample) |
| WO (1) | WO2012031017A1 (enExample) |
Families Citing this family (17)
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| US8980876B2 (en) | 2010-10-28 | 2015-03-17 | The Procter & Gamble Company | Inhibition of microbial growth by aconitase inhibition |
| WO2013033370A1 (en) | 2011-08-31 | 2013-03-07 | Portola Pharmaceuticals, Inc. | Prevention and treatment of thrombosis in medically ill patients |
| JP6227878B2 (ja) * | 2012-03-16 | 2017-11-08 | ラクステラ・インコーポレイテッドＬｕｘｔｅｒａ，Ｉｎｃ． | 光インターポーザのための方法及びシステム |
| US9200268B2 (en) | 2012-12-27 | 2015-12-01 | Portola Pharmaceuticals, Inc. | Compounds and methods for purification of serine proteases |
| US20140346397A1 (en) | 2012-12-27 | 2014-11-27 | Portola Pharmaceuticals, Inc. | Compounds and methods for purification of serine proteases |
| CN104693114B (zh) * | 2013-12-10 | 2019-08-16 | 四川海思科制药有限公司 | 一种贝曲西班的改进的制备方法 |
| CN105085387A (zh) * | 2014-05-20 | 2015-11-25 | 四川海思科制药有限公司 | 贝曲西班盐及其制备方法和用途 |
| WO2017091757A1 (en) | 2015-11-24 | 2017-06-01 | Portola Pharmaceuticals, Inc. | Isotopically enriched betrixaban |
| CN106995405A (zh) * | 2016-01-25 | 2017-08-01 | 重庆医药工业研究院有限责任公司 | 一种贝曲西班马来酸盐无定型物及其制备方法 |
| US20190300483A1 (en) * | 2016-06-02 | 2019-10-03 | Dr. Reddy's Laboratories Limited | POLYMORPHS OF BETRlXABAN & ITS MALEATE SALT |
| EP3254674A1 (en) | 2016-06-08 | 2017-12-13 | Sandoz Ag | Pharmaceutical compositions of betrixaban maleate |
| EP3293174A1 (en) | 2016-09-09 | 2018-03-14 | Sandoz Ag | Crystalline salts of betrixaban |
| WO2018069936A1 (en) | 2016-10-13 | 2018-04-19 | Mylan Laboratories Limited | Polymorphs and solid dispersion of betrixaban and methods for the preparation thereof |
| CN107382897B (zh) * | 2017-07-10 | 2021-05-04 | 浙江宏元药业股份有限公司 | 一种贝曲西班的中间体及其制备方法和应用 |
| EP3510996A1 (en) * | 2018-01-11 | 2019-07-17 | Sandoz AG | Pharmaceutical compositions of betrixaban |
| CN108570003A (zh) * | 2018-06-01 | 2018-09-25 | 浙江宏元药业股份有限公司 | 一种贝曲西班马来酸盐的一水无定形及其制备方法 |
| CN113905715B (zh) | 2019-06-28 | 2025-04-15 | 宝洁公司 | 光增强处理方法 |
Family Cites Families (21)
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| GB9226238D0 (en) | 1992-12-16 | 1993-02-10 | Scherer Ltd R P | Encapsulation apparatus and process |
| US6140351A (en) | 1997-12-19 | 2000-10-31 | Berlex Laboratories, Inc. | Ortho-anthranilamide derivatives as anti-coagulants |
| US6844367B1 (en) | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| MXPA02006660A (es) * | 2000-01-07 | 2002-12-13 | Transform Pharmaceuticals Inc | Formacion, identificacion y analisis de diversas formas solidas de alto rendimiento. |
| AU2001245353A1 (en) | 2000-02-29 | 2001-09-12 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| US6627646B2 (en) | 2001-07-17 | 2003-09-30 | Sepracor Inc. | Norastemizole polymorphs |
| DE10322469A1 (de) | 2003-05-19 | 2004-12-16 | Bayer Healthcare Ag | Heterocyclische Verbindungen |
| US7696352B2 (en) | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| CN1968922A (zh) | 2004-06-18 | 2007-05-23 | 米伦纽姆医药公司 | 因子xa抑制剂 |
| KR101358574B1 (ko) * | 2005-11-08 | 2014-02-04 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | Ｘａ 인자 억제제, ｎ（5클로로2피리디닐）2［［4［（디메틸아미노）이미노메틸］벤조일］아미노］5메톡시벤자마이드의 약제학적 염 및 다형체 |
| TW200813017A (en) | 2006-05-05 | 2008-03-16 | Millennium Pharm Inc | Factor XA inhibitors |
| US20080051578A1 (en) | 2006-08-24 | 2008-02-28 | Georg Dahmann | Substituted biaryls, process for their manufacture and use thereof as medicaments |
| PT2404906E (pt) | 2006-11-02 | 2015-11-02 | Millennium Pharm Inc | Métodos de sintetizar sais farmacêuticos de um inibidor de fator xa |
| CA2913963A1 (en) | 2006-12-08 | 2008-06-19 | Millenium Pharmaceuticals, Inc. | Unit dose formulations and methods of treating thrombosis with an oral factor xa inhibitor |
| EP2114930A2 (en) | 2007-01-05 | 2009-11-11 | Millennium Pharmaceuticals, Inc. | Factor xa inhibitors |
| AU2008239659B2 (en) | 2007-04-13 | 2013-09-05 | Millennium Pharmaceuticals, Inc. | Combination anticoagulant therapy with a compound that acts as a factor Xa inhibitor |
| EP2586439A1 (en) * | 2007-05-02 | 2013-05-01 | Portola Pharmaceuticals, Inc. | Combination therapy with a compound acting as a platelet ADP receptor inhibitor |
| SI2915564T1 (sl) | 2007-09-28 | 2021-03-31 | Alexion Pharmaceuticals, Inc. | Antidoti za zaviralce dejavnika Ksa in postopki njihove uporabe |
| US8455439B2 (en) * | 2008-11-14 | 2013-06-04 | Portola Pharmaceuticals, Inc. | Antidotes for factor Xa inhibitors and methods of using the same in combination with blood coagulating agents |
| JP5766204B2 (ja) | 2009-12-17 | 2015-08-19 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 第Ｘａ因子阻害剤の合成方法 |
| AR082803A1 (es) | 2010-09-01 | 2013-01-09 | Portola Pharm Inc | Metodos y formulaciones para el tratamiento de la trombosis con betrixaban y un inhibidor de la glicoproteina p |
-
2011
- 2011-08-30 AR ARP110103159A patent/AR082804A1/es unknown
- 2011-08-30 TW TW100131157A patent/TW201221128A/zh unknown
- 2011-08-31 PT PT117574673T patent/PT2611779T/pt unknown
- 2011-08-31 ES ES11757467.3T patent/ES2603084T3/es active Active
- 2011-08-31 CA CA2810004A patent/CA2810004C/en not_active Expired - Fee Related
- 2011-08-31 NZ NZ60844211A patent/NZ608442A/en not_active IP Right Cessation
- 2011-08-31 US US13/223,023 patent/US8946269B2/en active Active
- 2011-08-31 AU AU2011295909A patent/AU2011295909B2/en not_active Ceased
- 2011-08-31 CN CN201180052042.4A patent/CN103261161B/zh not_active Expired - Fee Related
- 2011-08-31 JP JP2013527286A patent/JP2013536864A/ja active Pending
- 2011-08-31 WO PCT/US2011/050057 patent/WO2012031017A1/en not_active Ceased
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2013
- 2013-02-13 IL IL224698A patent/IL224698A/en active IP Right Grant
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2015
- 2015-09-24 JP JP2015187427A patent/JP2015232046A/ja active Pending
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2017
- 2017-11-16 JP JP2017221050A patent/JP2018024709A/ja active Pending
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2019
- 2019-04-23 JP JP2019081907A patent/JP2019135258A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012031017A1 (en) | 2012-03-08 |
| AR082804A1 (es) | 2013-01-09 |
| CA2810004A1 (en) | 2012-03-08 |
| AU2011295909B2 (en) | 2015-05-21 |
| PT2611779T (pt) | 2016-11-21 |
| JP2015232046A (ja) | 2015-12-24 |
| ES2603084T3 (es) | 2017-02-23 |
| EP2611779A1 (en) | 2013-07-10 |
| AU2011295909A1 (en) | 2013-04-04 |
| JP2013536864A (ja) | 2013-09-26 |
| NZ608442A (en) | 2015-04-24 |
| CN103261161A (zh) | 2013-08-21 |
| CN103261161B (zh) | 2016-04-27 |
| US8946269B2 (en) | 2015-02-03 |
| JP2018024709A (ja) | 2018-02-15 |
| TW201221128A (en) | 2012-06-01 |
| EP2611779B1 (en) | 2016-08-10 |
| JP2019135258A (ja) | 2019-08-15 |
| IL224698A (en) | 2017-01-31 |
| US20120071519A1 (en) | 2012-03-22 |
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