RU2389501C2 - Применение модифицированных циклоспоринов для лечения заболеваний, вызванных hcv - Google Patents
Применение модифицированных циклоспоринов для лечения заболеваний, вызванных hcv Download PDFInfo
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- RU2389501C2 RU2389501C2 RU2006110533/15A RU2006110533A RU2389501C2 RU 2389501 C2 RU2389501 C2 RU 2389501C2 RU 2006110533/15 A RU2006110533/15 A RU 2006110533/15A RU 2006110533 A RU2006110533 A RU 2006110533A RU 2389501 C2 RU2389501 C2 RU 2389501C2
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| US7671017B2 (en) | 2004-07-14 | 2010-03-02 | Novartis Ag | Use of a combination of cyclosporine and pegylated interferon for treating hepatitis C (HCV) |
| WO2006039164A2 (en) | 2004-09-29 | 2006-04-13 | Amr Technology, Inc. | Novel cyclosporin analogues and their pharmaceutical uses |
| EP1809656A4 (en) | 2004-09-29 | 2009-03-25 | Amr Technology Inc | CYCLOSPORINAL KINANALOGA AND ITS PHARMACEUTICAL APPLICATIONS |
| MX2007003387A (es) * | 2004-10-01 | 2007-05-23 | Debiopharm Sa | Uso de [d-meala]3-[etval]4-ciclosporina para el tratamiento de infeccion por hepatitis c y composicion farmaceutica que comprende la [d-meala]3-[etval]4-ciclosporina. |
| US7196161B2 (en) | 2004-10-01 | 2007-03-27 | Scynexis Inc. | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection |
| CA2583494C (en) * | 2004-10-01 | 2014-01-21 | Scynexis, Inc. | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis c infection |
| US7361636B2 (en) | 2004-10-06 | 2008-04-22 | Amr Technology, Inc. | Cyclosporin alkynes and their utility as pharmaceutical agents |
| DE602005010607D1 (de) | 2004-11-22 | 2008-12-04 | Astellas Pharma Inc | Zyklosporinanalog |
| KR20070089954A (ko) * | 2004-12-23 | 2007-09-04 | 노파르티스 아게 | 플라비비리대 치료용 화합물 |
| RU2007128099A (ru) | 2004-12-23 | 2009-01-27 | Новартис АГ (CH) | Композиции для лечения гепатита с |
| MX2007016068A (es) | 2005-06-17 | 2008-03-10 | Novartis Ag | Uso de sanglifehrina en hcv. |
| CN101316606B (zh) * | 2005-09-30 | 2015-05-27 | 西尼克斯公司 | 治疗和预防丙型肝炎感染的方法和药物组合物 |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンaのアリールアルキル及びヘテロアリールアルキル誘導体 |
| JP5517454B2 (ja) * | 2005-09-30 | 2014-06-11 | スシネキス インク | C型肝炎感染の治療及び予防のための方法及び医薬組成物 |
| AU2006306974B2 (en) | 2005-10-26 | 2011-09-22 | Astellas Pharma Inc. | New cyclic peptide compounds |
| 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 |
| US7696165B2 (en) | 2006-03-28 | 2010-04-13 | Albany Molecular Research, Inc. | Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders |
| ATE502633T1 (de) | 2006-05-19 | 2011-04-15 | Scynexis Inc | Cyclosporins zur behandlung und vorbeugung von augenerkrankungen |
| CN101502196A (zh) * | 2006-06-02 | 2009-08-05 | 克洛德·安妮·佩里西恩 | 激活电子的管理 |
| CN101557819A (zh) * | 2006-10-12 | 2009-10-14 | 诺瓦提斯公司 | 修饰的环孢素的用途 |
| US7576057B2 (en) | 2006-11-20 | 2009-08-18 | Scynexis, Inc. | Cyclic peptides |
| US8450281B2 (en) * | 2007-01-04 | 2013-05-28 | Debiopharm S.A. | Non-immunosuppressive cyclosporin for treatment of Ullrich congenital muscular dystrophy |
| ES2396170T3 (es) * | 2007-05-02 | 2013-02-19 | Astellas Pharma Inc. | Nuevos compuestos péptídicos ciclicos |
| EP2193807A4 (en) * | 2007-08-24 | 2012-09-12 | Univ Sapporo Medical | BINDING PROTEIN AT CYCLOSPORIN A |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| CN102083852A (zh) * | 2008-06-06 | 2011-06-01 | 西尼克斯公司 | 环孢菌素类似物及其在治疗hcv感染中的应用 |
| JP5726733B2 (ja) * | 2008-07-30 | 2015-06-03 | シクロフィリン ファーマシューティカルズ コープ. | 非免疫抑制性シクロスポリン類似体分子 |
| CN102164947A (zh) * | 2008-09-24 | 2011-08-24 | 安斯泰来制药有限公司 | 肽化合物及其制备方法 |
| WO2010052559A1 (en) * | 2008-11-06 | 2010-05-14 | Debio Recherche Pharmaceutique S.A. | Cycloundecadepsipeptide compounds and use of said compounds as a medicament |
| JP5780969B2 (ja) * | 2008-12-31 | 2015-09-16 | サイネクシス,インコーポレーテッド | シクロスポリンaの誘導体 |
| US8367618B2 (en) * | 2009-01-30 | 2013-02-05 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues for preventing or treating hepatitis C infection |
| US8481483B2 (en) | 2009-02-19 | 2013-07-09 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US8349312B2 (en) | 2009-07-09 | 2013-01-08 | Enanta Pharmaceuticals, Inc. | Proline substituted cyclosporin analogues |
| US8685917B2 (en) | 2009-07-09 | 2014-04-01 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US8367053B2 (en) | 2009-07-09 | 2013-02-05 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US20110117055A1 (en) | 2009-11-19 | 2011-05-19 | Macdonald James E | Methods of Treating Hepatitis C Virus with Oxoacetamide Compounds |
| CN102869367A (zh) | 2009-12-09 | 2013-01-09 | 西尼克斯公司 | 新颖的环肽 |
| US8623814B2 (en) | 2010-02-23 | 2014-01-07 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| WO2012045704A1 (en) | 2010-10-05 | 2012-04-12 | Novartis Ag | New treatments of hepatitis c virus infection |
| US20130251678A1 (en) | 2010-11-30 | 2013-09-26 | Novartis Ag | Bid dosage regimen for deb025 |
| JO3337B1 (ar) | 2010-12-13 | 2019-03-13 | Debiopharm Sa | تركيبات صيدلية تشمل أليسبوريفير |
| HRP20190096T1 (hr) | 2010-12-15 | 2019-02-22 | Contravir Pharmaceuticals, Inc. | Molekule analoga ciklosporina modificirani na amino kiselini 1 i 3 |
| KR20140007927A (ko) | 2011-03-31 | 2014-01-20 | 노파르티스 아게 | C형 간염 바이러스 감염을 치료하기 위한 알리스포리비르 |
| BR112013024809A2 (pt) | 2011-04-01 | 2016-09-06 | Novartis Ag | tratamento para infecção com vírus de hepatite b sozinho ou em combinação com vírus de hepatite delta e doenças do fígado associadas |
| SG10201602184TA (en) | 2011-04-13 | 2016-04-28 | Novartis Ag | Treatment of hepatitis c virus infection with alisporivir |
| CA2850052A1 (en) | 2011-09-27 | 2013-04-04 | Novartis Ag | Alisporivr for treatment of hepatis c virus infection |
| WO2013169616A1 (en) | 2012-05-07 | 2013-11-14 | Novartis Ag | Pharmacokinetic modulation with alisporivir |
| JP2015519368A (ja) | 2012-06-01 | 2015-07-09 | アラーガン インコーポレイテッドAllergan,Incorporated | シクロスポリンa類似体 |
| US8906853B2 (en) | 2012-11-28 | 2014-12-09 | Enanta Pharmaceuticals, Inc. | [N-Me-4-hydroxyleucine]-9-cyclosporin analogues for treatment and prevention of hepatitis C infection |
| WO2015008223A1 (en) | 2013-07-17 | 2015-01-22 | Novartis Ag | Treatment of hepatitis c virus infection with alisporivir and ribavirin |
| WO2015031381A1 (en) | 2013-08-26 | 2015-03-05 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues for preventing or treating hepatitis c |
| WO2015136455A1 (en) | 2014-03-13 | 2015-09-17 | Novartis Ag | New treatments of hepatitis c virus infection |
| US9669095B2 (en) | 2014-11-03 | 2017-06-06 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues for preventing or treating hepatitis C infection |
| WO2016112321A1 (en) | 2015-01-08 | 2016-07-14 | Allergan, Inc. | Cyclosporin derivatives wherein the mebmt sidechain has been cyclized |
| WO2022043678A1 (en) * | 2020-08-24 | 2022-03-03 | Nanomerics Limited | Viral inhibitors |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5994299A (en) * | 1996-12-24 | 1999-11-30 | Rhone-Poulenc Rorer, S.A. | Cyclosporin compounds, their preparation and the pharmaceutical compositions which contain them |
| WO1999062540A1 (en) * | 1998-06-02 | 1999-12-09 | Novartis Ag | Use of cyclosporins in the treatment of inflammatory autoimmune diseases |
| WO2002032447A2 (en) * | 2000-10-19 | 2002-04-25 | Fujisawa Pharmaceutical Co., Ltd. | Cell damage inhibitor |
| US20020102279A1 (en) * | 1997-09-02 | 2002-08-01 | Kenji Chiba | Compositions and methods of using compositions with accelerated lymphocyte homing immunosuppressive properties |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639724A (en) * | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
| JP2514950B2 (ja) | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質,その製造法および中間体 |
| KR0148748B1 (ko) | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | 사이클로스포린을 함유하는 약학조성물 |
| DE69124459T3 (de) * | 1990-11-02 | 2001-05-31 | Novartis Ag, Basel | Zyklosporine |
| US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| US6174868B1 (en) * | 1992-09-10 | 2001-01-16 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of hepatitis C virus-associated diseases |
| DK0627406T3 (da) | 1992-10-21 | 1999-07-12 | Taito Co | 2-Amino-1,3-propandiolforbindelser og immunundertrykkende midler |
| KR960705579A (ko) | 1993-11-10 | 1996-11-08 | 에릭에스. 딕커 | 개선된 인터페론 중합체 결합체(Improved interferon polymer conjugates) |
| KR100358922B1 (ko) | 1994-08-22 | 2003-01-24 | 미쯔비시 웰 파마 가부시키가이샤 | 벤젠화합물및그의의약으로서의용도 |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| JP3786447B2 (ja) * | 1995-03-31 | 2006-06-14 | エーザイ株式会社 | C型肝炎の予防・治療剤 |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| FR2757520B1 (fr) | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derive de cyclosporine, sa preparation et les compositions pharmaceutiques qui le contiennent |
| FR2757522B1 (fr) | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| CN1290819C (zh) | 1997-04-04 | 2006-12-20 | 三菱制药株式会社 | 2-氨基丙烷-1,3-二醇化合物、其作为医药的用途及其合成中间体 |
| AU759480B2 (en) | 1998-07-01 | 2003-04-17 | Debiopharm S.A. | Novel cyclosporin with improved activity profile |
| BR0112484A (pt) | 2000-07-13 | 2003-09-23 | Sankyo Co | Composto ou um seu sal, éster ou outro derivado farmacologicamente aceitável, composição farmacêutica, uso de um composto ou de um seu sal, éster ou outro derivado farmacologicamente aceitável, e, processo para a preparação do mesmo |
| AU8533101A (en) | 2000-08-31 | 2002-03-13 | Merck & Co Inc | Phosphate derivatives as immunoregulatory agents |
| JP2002125683A (ja) * | 2000-10-27 | 2002-05-08 | Tokyoto Igaku Kenkyu Kiko | インターフェロンの有効性を予測する方法並びにそれに用いられるプライマー及びプローブ |
| JP4012823B2 (ja) | 2001-03-26 | 2007-11-21 | ノバルティス アクチエンゲゼルシャフト | 2−アミノ−誘導体 |
| JP2002316985A (ja) | 2001-04-20 | 2002-10-31 | Sankyo Co Ltd | ベンゾチオフェン誘導体 |
| BRPI0212894B8 (pt) | 2001-09-27 | 2021-05-25 | Kyorin Seiyaku Kk | composto ou sal do mesmo farmaceuticamente aceitável e composição farmacêutica |
| DE60235900D1 (de) | 2001-09-27 | 2010-05-20 | Kyorin Seiyaku Kk | Osuppressivum |
| AU2003207567B2 (en) | 2002-01-18 | 2008-01-24 | Merck Sharp & Dohme Corp. | Edg receptor agonists |
| US7351725B2 (en) | 2002-01-18 | 2008-04-01 | Merck & Co., Inc. | N-(benzyl)aminoalkylcarboxylates, phosphinates, phosphonates and tetrazoles as Edg receptor agonists |
| US20030213603A1 (en) * | 2002-05-14 | 2003-11-20 | Fisher David B. | Dual use extension apparatus for a tool |
| KR20050035194A (ko) | 2002-06-28 | 2005-04-15 | 이데닉스 (케이만) 리미티드 | 플라비비리다에 감염 치료용 2'-c-메틸-3'-o-l-발린에스테르 리보푸라노실 사이티딘 |
| GB0313444D0 (en) | 2003-06-11 | 2003-07-16 | Midland Medical Technologies L | Modular dysplasia cup |
| GB0320638D0 (en) | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| MX2007003387A (es) | 2004-10-01 | 2007-05-23 | Debiopharm Sa | Uso de [d-meala]3-[etval]4-ciclosporina para el tratamiento de infeccion por hepatitis c y composicion farmaceutica que comprende la [d-meala]3-[etval]4-ciclosporina. |
| RU2007128099A (ru) | 2004-12-23 | 2009-01-27 | Новартис АГ (CH) | Композиции для лечения гепатита с |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5994299A (en) * | 1996-12-24 | 1999-11-30 | Rhone-Poulenc Rorer, S.A. | Cyclosporin compounds, their preparation and the pharmaceutical compositions which contain them |
| US20020102279A1 (en) * | 1997-09-02 | 2002-08-01 | Kenji Chiba | Compositions and methods of using compositions with accelerated lymphocyte homing immunosuppressive properties |
| WO1999062540A1 (en) * | 1998-06-02 | 1999-12-09 | Novartis Ag | Use of cyclosporins in the treatment of inflammatory autoimmune diseases |
| WO2002032447A2 (en) * | 2000-10-19 | 2002-04-25 | Fujisawa Pharmaceutical Co., Ltd. | Cell damage inhibitor |
Non-Patent Citations (2)
| Title |
|---|
| с.3-4. * |
| ЭНЦИКЛОПЕДИЯ ЛЕКАРСТВ. - М., 2001 РЛС с.758-759. ГРЭХАМ-СМИТ Д.Г. и др. Оксфордский справочник по клинической фармакологии и фармакотерапии. - М.: Медицина, 2000, с.25-26, 136-137 СЭНФОРД Дж. и др. Антимикробная терапия. - М.: Практика, 1996 с.142-150. * |
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