JP5820722B2 - シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 - Google Patents
シクロスポリン類似体及びｈｃｖ感染の治療におけるその使用 Download PDFInfo
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- JP5820722B2 JP5820722B2 JP2011512478A JP2011512478A JP5820722B2 JP 5820722 B2 JP5820722 B2 JP 5820722B2 JP 2011512478 A JP2011512478 A JP 2011512478A JP 2011512478 A JP2011512478 A JP 2011512478A JP 5820722 B2 JP5820722 B2 JP 5820722B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5964908P | 2008-06-06 | 2008-06-06 | |
| US61/059,649 | 2008-06-06 | ||
| PCT/US2009/003411 WO2010002428A2 (en) | 2008-06-06 | 2009-06-05 | Novel macrocyclic peptides |
Publications (3)
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|---|---|
| JP2011523952A JP2011523952A (ja) | 2011-08-25 |
| JP2011523952A5 JP2011523952A5 (enExample) | 2012-07-26 |
| JP5820722B2 true JP5820722B2 (ja) | 2015-11-24 |
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| US (1) | US9090671B2 (enExample) |
| EP (1) | EP2280989B1 (enExample) |
| JP (1) | JP5820722B2 (enExample) |
| CN (1) | CN102083852A (enExample) |
| CA (1) | CA2724523A1 (enExample) |
| WO (1) | WO2010002428A2 (enExample) |
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| MX2007003538A (es) * | 2004-10-01 | 2008-01-16 | Scynexis Inc | Derivados de ciclosporina 3-eter y 3-tioeter sustituidos para el tratamiento y prevencion de infeccion de hepatitis c. |
| CN101316859A (zh) * | 2005-09-30 | 2008-12-03 | 西尼克斯公司 | 用于治疗和预防病毒感染的环孢菌素a的芳基烷基和杂芳基烷基衍生物 |
| US8188052B2 (en) | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| EP2027761A1 (fr) * | 2006-06-02 | 2009-02-25 | Claude Annie Perrichon | Gestion des electrons actifs |
| CA2724523A1 (en) | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| WO2009148615A1 (en) * | 2008-06-06 | 2009-12-10 | Scynexis, Inc. | Cyclosporin analogs and their use in the treatment of hcv infections |
| AU2009334790B2 (en) | 2008-12-31 | 2016-09-08 | Scynexis, Inc. | Derivatives of cyclosporin A |
| WO2012103520A1 (en) | 2011-01-28 | 2012-08-02 | Board Of Regents Of The University Of Nebraska | Methods and compositions for modulating cyclophilin d |
| 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 |
| TW201639873A (zh) | 2015-01-08 | 2016-11-16 | 歐樂根公司 | Ｍｅｂｍｔ側鏈已環化之環孢菌素衍生物 |
| CN109485771A (zh) * | 2018-10-30 | 2019-03-19 | 焦作中维特品药业股份有限公司 | 一种交联聚维酮的制备方法 |
| JP7277222B2 (ja) | 2019-03-29 | 2023-05-18 | 出光興産株式会社 | 潤滑油組成物 |
| CA3152922A1 (en) * | 2019-10-12 | 2021-04-15 | Michael Peel | Treatment and prevention of nephrotoxin-induced kidney injuries |
| CN114230498B (zh) * | 2021-12-30 | 2023-11-17 | 湖北华世通生物医药科技有限公司 | β-(二甲氨基)乙基对甲苯磺酸巯酯盐酸盐的制备方法 |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US496193A (en) * | 1893-04-25 | Hot-air furnace | ||
| EP0194972B1 (en) * | 1985-03-11 | 1992-07-29 | Sandoz Ag | Novel cyclosporins |
| US4814323A (en) * | 1986-03-25 | 1989-03-21 | Andrieu J M | Process for the treatment and the prevention of AIDS and other disorders induced by the LAV/HTLV III virus |
| US4798823A (en) * | 1987-06-03 | 1989-01-17 | Merck & Co., Inc. | New cyclosporin analogs with modified "C-9 amino acids" |
| US4885276A (en) * | 1987-06-03 | 1989-12-05 | Merck & Co., Inc. | Cyclosporin analogs with modified "C-9 amino acids" |
| US4996193A (en) | 1989-03-03 | 1991-02-26 | The Regents Of The University Of California | Combined topical and systemic method of administration of cyclosporine |
| ES2095926T5 (es) * | 1990-11-02 | 2001-02-16 | Novartis Ag | Cyclosporins. |
| US5948693A (en) * | 1994-09-01 | 1999-09-07 | Wisconsin Alumni Research Foundation | Solid phase synthesis of immunosuppressive agents |
| WO1997004005A2 (de) * | 1995-07-17 | 1997-02-06 | C-Chem Ag | Cyclosporin-derivate mit anti-hiv-wirkung |
| JP3089350B2 (ja) * | 1995-11-20 | 2000-09-18 | ギルフォード ファーマシューティカルズ インコーポレイテッド | シクロフィリンロタマーゼ活性の阻害剤 |
| FR2757521B1 (fr) | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Nouveaux derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| 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 |
| FR2762843B1 (fr) * | 1997-04-30 | 1999-12-10 | Rhone Poulenc Rorer Sa | Nouveaux derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2772768B1 (fr) | 1997-12-19 | 2000-01-14 | Rhone Poulenc Rorer Sa | Nouveau procede de preparation de derives de cyclosporine |
| GB9811854D0 (en) * | 1998-06-02 | 1998-07-29 | Ciba Geigy Ag | Organic compounds |
| PT1086124E (pt) * | 1998-06-12 | 2004-04-30 | Chem Ag C | Ciclosporinas novas |
| FR2780061B1 (fr) * | 1998-06-22 | 2001-09-07 | Rhone Poulenc Rorer Sa | Nouveau procede de preparation de derives de cyclosporine |
| WO2000001715A1 (fr) | 1998-07-01 | 2000-01-13 | Debiopharm S.A. | Nouvelle cyclosporine ayant un profil d'activite ameliore |
| US6521595B1 (en) * | 1999-11-19 | 2003-02-18 | Lg Chemical, Ltd. | Nonimmunosuppressive [γ-hydroxy-methylleucine4] cyclosporin A, hair growth stimulator and external composition for skin using the same |
| US7015499B1 (en) * | 1999-12-01 | 2006-03-21 | D-Wave Systems, Inc. | Permanent readout superconducting qubit |
| HUP0202263A3 (en) | 1999-12-27 | 2003-02-28 | Japan Tobacco Inc | Benzimidazole, indole and imidazo-pyridine derivatives and pharmaceutical compositions containing them |
| KR100939155B1 (ko) * | 2000-07-21 | 2010-01-28 | 쉐링 코포레이션 | Ｃ형 간염 바이러스의 ｎｓ3-세린 프로테아제 억제제로서의신규한 펩티드 |
| EP1355916B1 (en) | 2001-01-22 | 2007-01-10 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| AR036081A1 (es) | 2001-06-07 | 2004-08-11 | Smithkline Beecham Corp | Compuesto de 1,2-dihidroquinolina, su uso para preparar una composicion farmaceutica, metodos para prepararlo y compuestos del acido 2-aminobenzoico n-alquilado de utilidad como intermediarios en dichos metodos |
| HRP20040541A2 (en) * | 2001-11-27 | 2004-10-31 | Anadys Pharmaceuticals | 3- -D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIMIDINE NUCLEOSIDES AND USES THEREOF |
| KR20040039622A (ko) | 2002-11-04 | 2004-05-12 | 주식회사 엘지생활건강 | 모발 성장 효과를 갖는 사이클로스포린 3 위치 유도체를유효성분으로 하는 모발 성장 촉진제 |
| US6987090B2 (en) * | 2002-05-09 | 2006-01-17 | Lg Household & Health Care Ltd. | Use of 3-position cyclosporin derivatives for hair growth |
| EP1515971A2 (en) | 2002-06-17 | 2005-03-23 | Merck & Co., Inc. | Carbocyclic nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| MXPA04012802A (es) * | 2002-06-28 | 2005-04-19 | Idenix Cayman Ltd | Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. |
| WO2004007512A2 (en) | 2002-07-16 | 2004-01-22 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| US7148226B2 (en) | 2003-02-21 | 2006-12-12 | Agouron Pharmaceuticals, Inc. | Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same |
| GB0307891D0 (en) | 2003-04-04 | 2003-05-14 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| US20050009877A1 (en) | 2003-05-15 | 2005-01-13 | Henry Lu | Methods of identifying HCV NS5B polymerase inhibitors and their uses |
| GB0320638D0 (en) * | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| GB0323845D0 (en) | 2003-10-10 | 2003-11-12 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| EP1765330A4 (en) | 2004-03-01 | 2007-10-17 | Viropharma Inc | PYRANOINDOLE DERIVATIVES AND USE THEREOF FOR THE TREATMENT OF DISEASE OR INFECTION CAUSED BY HEPATITIS C VIRUS |
| GB0413087D0 (en) | 2004-06-11 | 2004-07-14 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| AU2005267421B2 (en) | 2004-06-24 | 2010-06-03 | Merck Sharp & Dohme Corp. | Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection |
| AU2005261838A1 (en) * | 2004-07-13 | 2006-01-19 | Novartis Ag | Cyclosporins to treat Alzheimer's disease |
| EP1778272B1 (en) | 2004-07-14 | 2011-02-09 | Novartis AG | Use of a combination of cyclosporin and pegylated interferons for treating hepatitis c (hcv) |
| GB0416396D0 (en) | 2004-07-22 | 2004-08-25 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| NZ552874A (en) | 2004-08-18 | 2010-04-30 | Pfizer | Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same |
| 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 |
| JP4892486B2 (ja) | 2004-10-01 | 2012-03-07 | デビオファーム ソシエテ アノニム | Ｃ型肝炎感染の治療のための［ｄ−ｍｅａｌａ］３−［ｅｔｖａｌ］４−シクロスポリンの使用、及び当該［ｄ−ｍｅａｌａ］３−［ｅｔｖａｌ］４−シクロスポリンを含む医薬組成物 |
| CN101068829B (zh) * | 2004-10-01 | 2012-05-30 | 西尼克斯公司 | 用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 |
| MX2007003538A (es) * | 2004-10-01 | 2008-01-16 | Scynexis Inc | Derivados de ciclosporina 3-eter y 3-tioeter sustituidos para el tratamiento y prevencion de infeccion de hepatitis c. |
| JP2008515886A (ja) | 2004-10-06 | 2008-05-15 | 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およびそれらの医用薬剤としての有用性 |
| JP2008517912A (ja) | 2004-10-21 | 2008-05-29 | メルク エンド カムパニー インコーポレーテッド | ＲＮＡ依存性ＲＮＡウイルス感染治療用フッ素化ピロロ［２，３−ｄ］ピリミジンヌクレオシド |
| US7662809B2 (en) | 2004-10-26 | 2010-02-16 | Istituto Di Richerche Di Biologia Molecolare P Angeletti Spa | Tetracyclic indole derivatives as antiviral agents |
| BRPI0519355A2 (pt) | 2004-12-23 | 2009-01-20 | Novartis Ag | compostos para tratamento contra flaviviridae |
| EP1830871A1 (en) | 2004-12-23 | 2007-09-12 | Novartis AG | Compositions for hcv treatment |
| GB0518390D0 (en) | 2005-09-09 | 2005-10-19 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7473688B2 (en) * | 2005-09-13 | 2009-01-06 | Bristol-Myers Squibb Company | Indolobenzazepine HCV NS5B inhibitors |
| WO2007041632A2 (en) * | 2005-09-30 | 2007-04-12 | Scynexis, Inc. | Methods and pharmaceutical compositions for the treatment and prevention of hepatitis c infection |
| CN101316859A (zh) * | 2005-09-30 | 2008-12-03 | 西尼克斯公司 | 用于治疗和预防病毒感染的环孢菌素a的芳基烷基和杂芳基烷基衍生物 |
| US8188052B2 (en) | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| US7576057B2 (en) * | 2006-11-20 | 2009-08-18 | Scynexis, Inc. | Cyclic peptides |
| WO2008127613A1 (en) | 2007-04-11 | 2008-10-23 | Scynexis, Inc. | New pharmaceutical compositions |
| WO2008143996A1 (en) | 2007-05-18 | 2008-11-27 | Scynexis, Inc. | New chemical processes |
| WO2009148615A1 (en) * | 2008-06-06 | 2009-12-10 | Scynexis, Inc. | Cyclosporin analogs and their use in the treatment of hcv infections |
| CA2724523A1 (en) | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| AU2009334790B2 (en) * | 2008-12-31 | 2016-09-08 | Scynexis, Inc. | Derivatives of cyclosporin A |
| RU2011127079A (ru) | 2009-01-07 | 2013-02-20 | Сайнексис, Инк. | Комбинация производного циклоспорина и нуклеозидов для лечения инфекции вирусом гепатита с |
| CA2750227A1 (en) | 2009-01-07 | 2010-07-15 | Scynexis, Inc. | Cyclosporine derivative for use in the treatment of hcv and hiv infection |
| CA2782898A1 (en) | 2009-12-09 | 2011-06-16 | Scynexis, Inc. | Novel cyclic peptides |
-
2009
- 2009-06-05 CA CA2724523A patent/CA2724523A1/en not_active Abandoned
- 2009-06-05 US US12/479,633 patent/US9090671B2/en not_active Expired - Fee Related
- 2009-06-05 CN CN2009801261909A patent/CN102083852A/zh active Pending
- 2009-06-05 EP EP09773881.9A patent/EP2280989B1/en not_active Not-in-force
- 2009-06-05 JP JP2011512478A patent/JP5820722B2/ja not_active Expired - Fee Related
- 2009-06-05 WO PCT/US2009/003411 patent/WO2010002428A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CN102083852A (zh) | 2011-06-01 |
| US9090671B2 (en) | 2015-07-28 |
| US20090312300A1 (en) | 2009-12-17 |
| EP2280989A2 (en) | 2011-02-09 |
| WO2010002428A3 (en) | 2010-03-11 |
| CA2724523A1 (en) | 2010-01-07 |
| EP2280989B1 (en) | 2016-02-10 |
| JP2011523952A (ja) | 2011-08-25 |
| WO2010002428A2 (en) | 2010-01-07 |
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