DK2427467T3 - Triptolid prodrugs - Google Patents
Triptolid prodrugs Download PDFInfo
- Publication number
- DK2427467T3 DK2427467T3 DK10719188.4T DK10719188T DK2427467T3 DK 2427467 T3 DK2427467 T3 DK 2427467T3 DK 10719188 T DK10719188 T DK 10719188T DK 2427467 T3 DK2427467 T3 DK 2427467T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- cancer
- formula
- triptolide
- alkyl
- Prior art date
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- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical compound O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](O)[C@]21[C@H]3O1 DFBIRQPKNDILPW-CIVMWXNOSA-N 0.000 title description 104
- 229940002612 prodrug Drugs 0.000 title description 49
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- -1 pyrrolidino, piperidino, piperazino Chemical group 0.000 claims description 19
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Landscapes
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| US17624909P | 2009-05-07 | 2009-05-07 | |
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| ES2902651T3 (es) * | 2012-08-23 | 2022-03-29 | Senestech Inc | Reducción de la capacidad reproductiva de mamíferos |
| 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 |
| CN109942665B (zh) * | 2018-04-02 | 2021-04-06 | 欣凯医药化工中间体（上海）有限公司 | 雷公藤内酯醇衍生物及其制备方法和应用 |
| 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 |
| CA3112171A1 (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 |
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| 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 |
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| 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 |
| KR101016969B1 (ko) * | 2001-12-21 | 2011-02-25 | 에이자이 아이엔씨. | 알콜 및 페놀의 수용성 포스포노옥시메틸 유도체를제조하는 방법 |
| AU2003243351B2 (en) | 2002-05-31 | 2009-04-30 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| CN100398544C (zh) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | 高免疫抑制活性的水溶性雷公藤内酯醇衍生物及其应用 |
| 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 |
| US7820834B2 (en) | 2003-12-24 | 2010-10-26 | Pharmagenesis, Inc. | Triptolide 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 |
| ES2385716T3 (es) | 2004-03-02 | 2012-07-30 | Pharmagenesis, Inc. | Derivados en el anillo de lactona de triptolida como inmunomoduladores y agentes anticáncer |
| 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 |
| EP2079699A1 (en) * | 2006-07-25 | 2009-07-22 | Envivo Pharmaceuticals, Inc. | Quinoline derivatives |
| CN101622263B (zh) * | 2007-03-06 | 2013-05-29 | 卫材R&D管理有限公司 | 稳定性被改善的含有磷酸氯甲酯衍生物的组合物及其制备方法 |
| 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 JP JP2012510027A patent/JP6000122B2/ja active Active
- 2010-05-07 MX MX2011011776A patent/MX2011011776A/es active IP Right Grant
- 2010-05-07 BR BRPI1014802A patent/BRPI1014802B8/pt active IP Right Grant
- 2010-05-07 AU AU2010245669A patent/AU2010245669B2/en active Active
- 2010-05-07 EP EP10719188.4A patent/EP2427467B1/en 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 DK DK10719188.4T patent/DK2427467T3/en active
- 2010-05-07 MY MYPI2011005335A patent/MY160392A/en unknown
- 2010-05-07 CA CA2760953A patent/CA2760953C/en active Active
- 2010-05-07 SG SG2011081122A patent/SG175885A1/en unknown
- 2010-05-07 KR KR1020117029123A patent/KR101821823B1/ko active Active
- 2010-05-07 WO PCT/US2010/034117 patent/WO2010129918A1/en not_active Ceased
- 2010-05-07 ES ES10719188.4T patent/ES2552163T3/es active Active
- 2010-05-07 PL PL10719188T patent/PL2427467T3/pl unknown
- 2010-05-07 EA EA201190293A patent/EA021135B1/ru unknown
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2014
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2016
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2427467B1 (en) | 2015-08-05 |
| MX2011011776A (es) | 2012-08-03 |
| BRPI1014802A2 (pt) | 2016-04-05 |
| CA2760953C (en) | 2017-05-30 |
| ES2552163T3 (es) | 2015-11-26 |
| KR101821823B1 (ko) | 2018-01-24 |
| EA201190293A1 (ru) | 2012-11-30 |
| EA021135B1 (ru) | 2015-04-30 |
| JP2016065099A (ja) | 2016-04-28 |
| CN102596977B (zh) | 2016-06-29 |
| EP2427467A1 (en) | 2012-03-14 |
| AU2010245669A1 (en) | 2011-12-01 |
| WO2010129918A8 (en) | 2011-01-20 |
| JP2014185181A (ja) | 2014-10-02 |
| WO2010129918A1 (en) | 2010-11-11 |
| PT2427467E (pt) | 2015-11-19 |
| AU2010245669B2 (en) | 2015-11-26 |
| PL2427467T3 (pl) | 2016-04-29 |
| HK1168107A1 (en) | 2012-12-21 |
| KR20120015339A (ko) | 2012-02-21 |
| JP2012526148A (ja) | 2012-10-25 |
| JP6000122B2 (ja) | 2016-09-28 |
| CN102596977A (zh) | 2012-07-18 |
| SG175885A1 (en) | 2011-12-29 |
| US20120238529A1 (en) | 2012-09-20 |
| BRPI1014802B1 (pt) | 2020-09-24 |
| US8507552B2 (en) | 2013-08-13 |
| CA2964631A1 (en) | 2010-11-11 |
| BRPI1014802B8 (pt) | 2021-05-25 |
| CA2760953A1 (en) | 2010-11-11 |
| MY160392A (en) | 2017-03-15 |
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