KR100992850B1 - 시클로스포린 유사체 혼합물 및 면역조절제로서 이들의 용도 - Google Patents
시클로스포린 유사체 혼합물 및 면역조절제로서 이들의 용도 Download PDFInfo
- Publication number
- KR100992850B1 KR100992850B1 KR1020047005721A KR20047005721A KR100992850B1 KR 100992850 B1 KR100992850 B1 KR 100992850B1 KR 1020047005721 A KR1020047005721 A KR 1020047005721A KR 20047005721 A KR20047005721 A KR 20047005721A KR 100992850 B1 KR100992850 B1 KR 100992850B1
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- Prior art keywords
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- cyclosporin
- mixture
- isomer
- pharmaceutical composition
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| US34620101P | 2001-10-19 | 2001-10-19 | |
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| JP2005511538A (ja) * | 2001-10-19 | 2005-04-28 | アイソテクニカ インコーポレーテッド | シクロスポリン類似体混合物及びそれらの免疫調節剤としての使用 |
| CN100334106C (zh) | 2001-10-19 | 2007-08-29 | 伊索泰克尼卡股份有限公司 | 环孢菌素类似物的合成 |
| JP2006524232A (ja) | 2003-03-17 | 2006-10-26 | アルバニー モレキュラー リサーチ インコーポレーティッド | 新規サイクロスポリン |
| TW200505946A (en) * | 2003-04-08 | 2005-02-16 | Hoffmann La Roche | Process for preparation of cyclosporin a analog |
| JP2008514701A (ja) | 2004-09-29 | 2008-05-08 | エーエムアール テクノロジー インコーポレイテッド | シクロスポリンアルキン類似体およびそれらの薬学的使用 |
| US7511013B2 (en) | 2004-09-29 | 2009-03-31 | Amr Technology, Inc. | Cyclosporin analogues and their pharmaceutical uses |
| WO2006041631A2 (en) | 2004-10-06 | 2006-04-20 | Amr Technology, Inc. | Novel cyclosporin alkynes and their utility as pharmaceutical agents |
| WO2006063470A1 (en) * | 2004-12-17 | 2006-06-22 | Isotechnika Inc. | Metabolites of cyclosporin analogs |
| ES2557477T3 (es) * | 2005-10-26 | 2016-01-26 | Astellas Pharma Inc. | Nuevos compuestos peptídicos cíclicos |
| US7696165B2 (en) | 2006-03-28 | 2010-04-13 | Albany Molecular Research, Inc. | Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders |
| US7696166B2 (en) | 2006-03-28 | 2010-04-13 | Albany Molecular Research, Inc. | Use of cyclosporin alkyne/alkene analogues for preventing or treating viral-induced disorders |
| CN101687012A (zh) * | 2007-05-02 | 2010-03-31 | 安斯泰来制药有限公司 | 新的环肽化合物 |
| MX2010003364A (es) | 2007-10-08 | 2010-07-06 | Lux Biosciences Inc | Composiciones oftalmicas que comprenden inhibidores de calcineurina o inhibidores de mtor. |
| RU2361604C1 (ru) * | 2007-10-29 | 2009-07-20 | Федеральное агентство по высокотехнологичной медицинской помощи Федеральное государственное учреждение "Уральский научно-исследовательский институт дерматовенерологии и иммунопатологии" (ФГУ УрНИИДВиИ Росмедтехнологий) | Способ лечения атопического дерматита |
| US9017725B2 (en) | 2009-06-09 | 2015-04-28 | Aurinia Pharmaceuticals Inc. | Topical drug delivery systems for ophthalmic use |
| GB0912584D0 (en) * | 2009-07-20 | 2009-08-26 | Ucl Business Plc | Cyclosporin conjugates |
| PL2651965T3 (pl) | 2010-12-15 | 2019-04-30 | Contravir Pharmaceuticals Inc | Cząsteczki analogów cyklosporyny modyfikowane w aminokwasach 1 i 3 |
| GB201222455D0 (en) * | 2012-12-13 | 2013-01-30 | Perioc Ltd | Novel pharmaceutical formulations and their use in the treatment of periodontaldisease |
| WO2018102565A1 (en) * | 2016-11-30 | 2018-06-07 | Schrödinger, Inc. | Graphical user interface for chemical transition state calculations |
| EP3551047A1 (en) | 2016-12-07 | 2019-10-16 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| WO2018106928A1 (en) | 2016-12-08 | 2018-06-14 | Contravir Pharmaceuticals, Inc. | Treatment and prevention of hbv diseases by cyclosporine analogue molecules modified at amino acides 1 and 3 |
| CA3046023A1 (en) | 2016-12-14 | 2018-06-21 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunosuppressant |
| US10286036B2 (en) * | 2017-05-12 | 2019-05-14 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| US20190224275A1 (en) | 2017-05-12 | 2019-07-25 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| US20230041197A1 (en) | 2018-06-20 | 2023-02-09 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
| KR20220158761A (ko) * | 2020-03-26 | 2022-12-01 | 파사이트 메디컬 테크놀로지 (상하이) 컴퍼니 리미티드 | 사이클로스포린 유도체의 제조 |
| EP4201952A1 (en) | 2021-12-21 | 2023-06-28 | Curia Spain, S.A.U. | Process for the controlled synthesis of voclosporin |
| US20250353880A1 (en) * | 2022-09-09 | 2025-11-20 | Dr. Reddy’S Laboratories Limited | Improved process for the preparation of voclosporin |
| IT202300001056A1 (it) * | 2023-01-25 | 2024-07-25 | Procos Spa | Nuovo processo per la preparazione di voclosporina amorfa |
| IT202300001116A1 (it) * | 2023-01-25 | 2024-07-25 | Indena Spa | Processo per la preparazione di un intermedio utile per la sintesi di voclosporina |
| WO2025119925A1 (en) | 2023-12-05 | 2025-06-12 | Medichem, S.A. | Process for preparing voclosporin |
| WO2025141456A1 (en) * | 2023-12-27 | 2025-07-03 | Indena S.P.A. | Process for the preparation of voclosporin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999018120A1 (en) * | 1997-10-08 | 1999-04-15 | Isotechnika Inc. | Deuterated cyclosporine analogs and their use as immunomodulating agents |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4278545A (en) * | 1979-09-12 | 1981-07-14 | The Bendix Corporation | Apparatus for separating solids and liquid components |
| CH670644A5 (enExample) * | 1986-12-18 | 1989-06-30 | Lonza Ag | |
| US5162540A (en) * | 1986-12-18 | 1992-11-10 | Lonza Ltd. | Process for the production of (+) biotin |
| DE3884470T2 (de) * | 1987-06-17 | 1994-03-10 | Sandoz Ag | Cyclosporine und deren Benutzung als Arzneimittel. |
| US5972630A (en) * | 1991-08-19 | 1999-10-26 | Dade Behring Marburg Gmbh | Homogeneous immunoassays using enzyme inhibitors |
| GB9204466D0 (en) * | 1992-03-02 | 1992-04-15 | Sandoz Ltd | Improvements in or relating to organic compounds |
| US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
| US5750510A (en) * | 1997-04-04 | 1998-05-12 | Abbott Laboratories | 3-descladinose-2,3-anhydroerythromycin derivatives |
| BR9713811A (pt) * | 1996-06-19 | 2004-03-02 | Novartis Ag | Preparações de cápsula macia contendo ciclosporina |
| US5939406A (en) * | 1997-07-21 | 1999-08-17 | Wisconsin Alumni Research Foundation | 18-substituted-19-nor-vitamin D compounds |
| CN100334106C (zh) * | 2001-10-19 | 2007-08-29 | 伊索泰克尼卡股份有限公司 | 环孢菌素类似物的合成 |
| JP2005511538A (ja) * | 2001-10-19 | 2005-04-28 | アイソテクニカ インコーポレーテッド | シクロスポリン類似体混合物及びそれらの免疫調節剤としての使用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2002331510A1 (en) | Cyclosporine analogue mixtures and their use as immunomodulating agents | |
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| HK1062567B (en) | Cyclosporine analogue mixtures and their use as immunomodulating agents |
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