EA021135B1 - Пролекарства триптолида - Google Patents
Пролекарства триптолида Download PDFInfo
- Publication number
- EA021135B1 EA021135B1 EA201190293A EA201190293A EA021135B1 EA 021135 B1 EA021135 B1 EA 021135B1 EA 201190293 A EA201190293 A EA 201190293A EA 201190293 A EA201190293 A EA 201190293A EA 021135 B1 EA021135 B1 EA 021135B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- formula
- cancer
- tryptolide
- mice
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Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17624909P | 2009-05-07 | 2009-05-07 | |
| PCT/US2010/034117 WO2010129918A1 (en) | 2009-05-07 | 2010-05-07 | Triptolide prodrugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201190293A1 EA201190293A1 (ru) | 2012-11-30 |
| EA021135B1 true EA021135B1 (ru) | 2015-04-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201190293A EA021135B1 (ru) | 2009-05-07 | 2010-05-07 | Пролекарства триптолида |
Country Status (17)
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|---|---|
| US (1) | US8507552B2 (OSRAM) |
| EP (1) | EP2427467B1 (OSRAM) |
| JP (3) | JP6000122B2 (OSRAM) |
| KR (1) | KR101821823B1 (OSRAM) |
| CN (1) | CN102596977B (OSRAM) |
| AU (1) | AU2010245669B2 (OSRAM) |
| BR (1) | BRPI1014802B8 (OSRAM) |
| CA (2) | CA2964631A1 (OSRAM) |
| DK (1) | DK2427467T3 (OSRAM) |
| EA (1) | EA021135B1 (OSRAM) |
| ES (1) | ES2552163T3 (OSRAM) |
| MX (1) | MX2011011776A (OSRAM) |
| MY (1) | MY160392A (OSRAM) |
| PL (1) | PL2427467T3 (OSRAM) |
| PT (1) | PT2427467E (OSRAM) |
| SG (1) | SG175885A1 (OSRAM) |
| WO (1) | WO2010129918A1 (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2753036C1 (ru) * | 2018-04-02 | 2021-08-11 | Цинкате Фармацеутикал Интермедиатес Ко., Лтд. | Производное триптолида, способ его получения и применение |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US9150600B2 (en) | 2009-05-07 | 2015-10-06 | Regents Of The University Of Minnesota | Triptolide prodrugs |
| KR20150059746A (ko) | 2012-08-23 | 2015-06-02 | 세네스텍 인코포레이티드 | 포유동물의 번식 능력을 감소시키는 방법 |
| WO2014047783A1 (zh) * | 2012-09-25 | 2014-04-03 | 鼎泓国际投资（香港）有限公司 | 含有雷公藤甲素及雷公藤甲素类衍生物和Bcl-2抑制剂的药物组合物及其应用 |
| WO2014167581A2 (en) * | 2013-04-01 | 2014-10-16 | Laurus Labs Private Limited | An improved process for the preparation of triptolide prodrugs |
| SG11201802915WA (en) * | 2015-09-11 | 2018-05-30 | Ys Ac Co Ltd | Cancer treatment composition combining anti-cd26 antibody and other anticancer agent |
| CN110551171B (zh) * | 2018-05-31 | 2021-07-27 | 欣凯医药化工中间体（上海）有限公司 | 一种雷公藤内酯醇衍生物的制备方法 |
| WO2020056174A1 (en) | 2018-09-13 | 2020-03-19 | Minneamrita Therapeutics, LLC | Triptolide and prodrugs thereof for use in methods to treat fibrosis, nash, and nafld |
| WO2021221179A1 (ja) * | 2020-04-28 | 2021-11-04 | 国立大学法人高知大学 | ヒト膵癌オルガノイドを用いたマウスモデルの樹立 |
| JP2023538424A (ja) | 2020-08-21 | 2023-09-07 | ルヤン コーポレイション | トリプトリドコンジュゲートおよびその使用 |
| CN115227829B (zh) * | 2022-02-22 | 2023-10-13 | 成都中医药大学 | 酸敏感性适配体雷公藤甲素偶联物及应用 |
| WO2024186320A1 (en) | 2023-03-09 | 2024-09-12 | Minneamrita Therapeutics Llc | Drug combination for treatment of pancreatic cancer |
| WO2024187139A1 (en) | 2023-03-09 | 2024-09-12 | Minneamrita Therapeutics Llc | Drug combination for treatment of gastric cancer |
| JP7759145B2 (ja) | 2023-03-09 | 2025-10-23 | ミネアムリタ セラピューティクス， エルエルシー | 胃癌の治療のための薬物の組み合わせ |
Citations (2)
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|---|---|---|---|---|
| EP1552829A1 (en) * | 2002-09-18 | 2005-07-13 | Farreach Lab. | Derivatives of triptolide having high immunosuppressive effect and high water solubility, and uses thereof |
| WO2008014602A1 (en) * | 2006-07-25 | 2008-02-07 | Envivo Pharmaceuticals, Inc. | Quinoline derivatives |
Family Cites Families (28)
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| US5843452A (en) | 1992-11-09 | 1998-12-01 | Pharmagenesis, Inc. | Immunotherapy composition and method |
| US5759550A (en) | 1993-05-06 | 1998-06-02 | Pharmagenesis, Inc. | Method for suppressing xenograft rejection |
| US5609991A (en) | 1995-02-10 | 1997-03-11 | Morton International, Inc. | Photoimageable composition having improved alkaline process resistance and tack-free surface for contact imaging |
| US5663335A (en) | 1996-03-01 | 1997-09-02 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| US5962516A (en) | 1997-02-28 | 1999-10-05 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| US6204257B1 (en) * | 1998-08-07 | 2001-03-20 | Universtiy Of Kansas | Water soluble prodrugs of hindered alcohols |
| US6548537B1 (en) | 1998-09-02 | 2003-04-15 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| AU764123B2 (en) | 1998-09-02 | 2003-08-07 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| AU3365800A (en) | 1999-02-16 | 2000-09-04 | Board Of Trustees Of The Leland Stanford Junior University | Combined therapy of diterpenoid triepoxides and trail for synergistic killing oftumor cells |
| AU5368699A (en) | 1999-04-16 | 2000-11-02 | Chengdu Diao Pharmaceutical Group Company Limited | Derivatives of triptolide, and preparation and uses thereof |
| US6294546B1 (en) | 1999-08-30 | 2001-09-25 | The Broad Of Trustees Of The Leland Stanford Junior University | Uses of diterpenoid triepoxides as an anti-proliferative agent |
| US6620843B2 (en) * | 2001-01-19 | 2003-09-16 | Pharmagenesis | Anticancer treatment using triptolide prodrugs |
| EP1390358A4 (en) * | 2001-03-15 | 2004-06-16 | Pharmagenesis Inc | AMINO ACID DERIVATIVES OF TRIPTOLIDE COMPOUNDS AS IMMUNOMODULATORS AND ANTICROPHES |
| KR20100101011A (ko) * | 2001-12-21 | 2010-09-15 | 에이자이 아이엔씨. | 알콜 및 페놀의 수용성 포스포노옥시메틸 유도체를 제조하는 방법 |
| CA2485794C (en) * | 2002-05-31 | 2012-10-16 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| WO2004058246A1 (en) | 2002-12-17 | 2004-07-15 | Pharmagenesis, Inc. | Triptolide derivatives as immunomodulator and anticancer agents |
| CN1223595C (zh) | 2002-12-27 | 2005-10-19 | 中国科学院上海药物研究所 | 雷公藤内酯醇衍生物及其应用 |
| US6943259B2 (en) | 2003-02-25 | 2005-09-13 | Pharmagenesis, Inc. | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| WO2005020887A2 (en) | 2003-06-27 | 2005-03-10 | Pharmagenesis, Inc. | Method for treatment of severe acute respiratory syndrome |
| WO2005062913A2 (en) | 2003-12-24 | 2005-07-14 | Pharmagenesis, Inc. | Triplide 5,6-derivatives as immunomodulators and anticancer agents |
| JP5252765B2 (ja) | 2003-12-26 | 2013-07-31 | 学校法人東京薬科大学 | 皮脂産生抑制剤及び皮脂腺発達抑制剤、並びに、皮膚外用剤 |
| AU2005218610B2 (en) | 2004-03-02 | 2011-08-18 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| US20070244080A1 (en) | 2004-06-25 | 2007-10-18 | Pharmagenesis, Inc. | Method for Treatment of Inflammatory Disorders Using Triptolide Compounds |
| WO2007025031A2 (en) * | 2005-08-24 | 2007-03-01 | Cephalon, Inc. | Prodrugs of indanone and tetralone compounds |
| CN101049300A (zh) | 2006-04-04 | 2007-10-10 | 中国科学院上海药物研究所 | 包含雷公藤内酯醇衍生物的药物组合物、其剂型和应用 |
| JP5221514B2 (ja) * | 2007-03-06 | 2013-06-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 安定性が改善されたクロロメチルフォスフェイト誘導体を含む組成物及びその製造方法 |
| FI20070574A0 (fi) * | 2007-07-30 | 2007-07-30 | Kuopion Yliopisto | Vesiliukoinen propofolin etylideenifosfaatti-aihiolääke |
| WO2009023201A1 (en) | 2007-08-16 | 2009-02-19 | Myelorx Llc | Rigid derivatives of triptolide as anticancer, immune suppressant, anti-fibrosis, and cns protectant agents |
-
2010
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- 2010-05-07 AU AU2010245669A patent/AU2010245669B2/en active Active
- 2010-05-07 MX MX2011011776A patent/MX2011011776A/es active IP Right Grant
- 2010-05-07 MY MYPI2011005335A patent/MY160392A/en unknown
- 2010-05-07 CN CN201080031839.1A patent/CN102596977B/zh active Active
- 2010-05-07 ES ES10719188.4T patent/ES2552163T3/es active Active
- 2010-05-07 PT PT107191884T patent/PT2427467E/pt unknown
- 2010-05-07 US US13/319,316 patent/US8507552B2/en active Active
- 2010-05-07 EA EA201190293A patent/EA021135B1/ru unknown
- 2010-05-07 DK DK10719188.4T patent/DK2427467T3/en active
- 2010-05-07 JP JP2012510027A patent/JP6000122B2/ja active Active
- 2010-05-07 KR KR1020117029123A patent/KR101821823B1/ko active Active
- 2010-05-07 CA CA2964631A patent/CA2964631A1/en not_active Abandoned
- 2010-05-07 CA CA2760953A patent/CA2760953C/en active Active
- 2010-05-07 BR BRPI1014802A patent/BRPI1014802B8/pt active IP Right Grant
- 2010-05-07 WO PCT/US2010/034117 patent/WO2010129918A1/en not_active Ceased
- 2010-05-07 EP EP10719188.4A patent/EP2427467B1/en active Active
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2014
- 2014-07-03 JP JP2014137661A patent/JP2014185181A/ja not_active Withdrawn
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2016
- 2016-01-08 JP JP2016002236A patent/JP2016065099A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1552829A1 (en) * | 2002-09-18 | 2005-07-13 | Farreach Lab. | Derivatives of triptolide having high immunosuppressive effect and high water solubility, and uses thereof |
| WO2008014602A1 (en) * | 2006-07-25 | 2008-02-07 | Envivo Pharmaceuticals, Inc. | Quinoline derivatives |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2753036C1 (ru) * | 2018-04-02 | 2021-08-11 | Цинкате Фармацеутикал Интермедиатес Ко., Лтд. | Производное триптолида, способ его получения и применение |
| RU2753036C9 (ru) * | 2018-04-02 | 2021-10-21 | Цинкaте Фaрмaцеутикaл Интермедиaтес Ко., Лтд. | Производное триптолида, способ его получения и применение |
Also Published As
| Publication number | Publication date |
|---|---|
| SG175885A1 (en) | 2011-12-29 |
| CN102596977A (zh) | 2012-07-18 |
| EP2427467A1 (en) | 2012-03-14 |
| KR101821823B1 (ko) | 2018-01-24 |
| BRPI1014802B8 (pt) | 2021-05-25 |
| HK1168107A1 (en) | 2012-12-21 |
| US8507552B2 (en) | 2013-08-13 |
| BRPI1014802B1 (pt) | 2020-09-24 |
| EP2427467B1 (en) | 2015-08-05 |
| DK2427467T3 (en) | 2015-11-09 |
| JP6000122B2 (ja) | 2016-09-28 |
| MX2011011776A (es) | 2012-08-03 |
| US20120238529A1 (en) | 2012-09-20 |
| CA2760953C (en) | 2017-05-30 |
| WO2010129918A8 (en) | 2011-01-20 |
| PT2427467E (pt) | 2015-11-19 |
| CA2964631A1 (en) | 2010-11-11 |
| MY160392A (en) | 2017-03-15 |
| EA201190293A1 (ru) | 2012-11-30 |
| KR20120015339A (ko) | 2012-02-21 |
| AU2010245669A1 (en) | 2011-12-01 |
| BRPI1014802A2 (pt) | 2016-04-05 |
| WO2010129918A1 (en) | 2010-11-11 |
| CA2760953A1 (en) | 2010-11-11 |
| JP2014185181A (ja) | 2014-10-02 |
| JP2012526148A (ja) | 2012-10-25 |
| ES2552163T3 (es) | 2015-11-26 |
| PL2427467T3 (pl) | 2016-04-29 |
| CN102596977B (zh) | 2016-06-29 |
| AU2010245669B2 (en) | 2015-11-26 |
| JP2016065099A (ja) | 2016-04-28 |
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