ES2278049T3 - Uso de inhibidores de proteasoma para tratar trastornos de ojo seco. - Google Patents
Uso de inhibidores de proteasoma para tratar trastornos de ojo seco. Download PDFInfo
- Publication number
- ES2278049T3 ES2278049T3 ES02771849T ES02771849T ES2278049T3 ES 2278049 T3 ES2278049 T3 ES 2278049T3 ES 02771849 T ES02771849 T ES 02771849T ES 02771849 T ES02771849 T ES 02771849T ES 2278049 T3 ES2278049 T3 ES 2278049T3
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- Prior art keywords
- alkyl
- eye
- dry eye
- formula
- compound
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 239000003207 proteasome inhibitor Substances 0.000 title claims abstract description 19
- 208000030533 eye disease Diseases 0.000 title description 2
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- 206010013774 Dry eye Diseases 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 238000009736 wetting Methods 0.000 claims abstract description 6
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- 150000001875 compounds Chemical class 0.000 claims description 26
- -1 morpholinylcarbonyl Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 14
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- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| WO2005099687A2 (en) * | 2004-04-09 | 2005-10-27 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US20060167106A1 (en) * | 2004-11-19 | 2006-07-27 | Mei Zhang | Compounds acting at the centrosome |
| US7465720B2 (en) | 2005-09-12 | 2008-12-16 | President And Fellows Of Harvard College | Proteasome inhibiting β-lactam compounds |
| KR101434522B1 (ko) * | 2005-11-09 | 2014-08-26 | 오닉스 세라퓨틱스, 인크. | 효소 저해를 위한 화합물 |
| US7691852B2 (en) | 2006-06-19 | 2010-04-06 | Onyx Therapeutics, Inc. | Compounds for enzyme inhibition |
| RS54847B2 (sr) | 2007-10-04 | 2019-09-30 | Onyx Therapeutics Inc | Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto-epoksida |
| JP5675629B2 (ja) | 2008-10-21 | 2015-02-25 | オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | ペプチドエポキシケトンを用いた併用療法 |
| AR075899A1 (es) | 2009-03-20 | 2011-05-04 | Onyx Therapeutics Inc | Tripeptidos epoxicetonas cristalinos inhibidores de proteasa |
| JP5919196B2 (ja) | 2009-11-13 | 2016-05-18 | オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 転移抑制のためのペプチドエポキシケトンの使用 |
| MA34133B1 (fr) | 2010-03-01 | 2013-04-03 | Onyx Therapeutics Inc | Composes pour inhibiteurs de l'immunoproteasome |
| WO2011136905A2 (en) | 2010-04-07 | 2011-11-03 | Onyx Therapeutics, Inc. | Crystalline peptide epoxyketone immunoproteasome inhibitor |
| US9126997B1 (en) | 2010-09-07 | 2015-09-08 | Northwestern University | Synergistic effect of glucocorticoid receptor agonists in combination with proteosome inhibitors for treating leukemia and myeloma |
| US20140105921A1 (en) | 2012-07-09 | 2014-04-17 | Onyx Therapeutics, Inc. | Prodrugs of Peptide Epoxy Ketone Protease Inhibitors |
| CN103893742B (zh) * | 2014-03-03 | 2016-01-20 | 中山大学中山眼科中心 | 含卵黄膜外层蛋白1在制备治疗干眼药物中的应用 |
| CN107151255A (zh) * | 2016-03-06 | 2017-09-12 | 复旦大学 | 硼酸类化合物及其制备方法和用途 |
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| US3991759A (en) | 1975-10-28 | 1976-11-16 | Alza Corporation | Method and therapeutic system for treating aqueous deficient dry eye |
| US4131651A (en) | 1977-10-25 | 1978-12-26 | Barnes-Hind Pharmaceuticals, Inc. | Treatment of dry eye |
| US4409205A (en) | 1979-03-05 | 1983-10-11 | Cooper Laboratories, Inc. | Ophthalmic solution |
| US4370325A (en) | 1979-03-30 | 1983-01-25 | Dermik Laboratories | Pharmaceutical compositions and method of treatment |
| US4744980A (en) | 1986-04-28 | 1988-05-17 | Holly Frank J | Ophthalmic solution for treatment of dry eye syndrome |
| US4883658A (en) | 1986-04-28 | 1989-11-28 | Holly Frank J | Ophthalmic solution for treatment of dry-eye syndrome |
| US4804539A (en) | 1986-07-28 | 1989-02-14 | Liposome Technology, Inc. | Ophthalmic liposomes |
| US4818537A (en) | 1986-10-21 | 1989-04-04 | Liposome Technology, Inc. | Liposome composition for treating dry eye |
| US4966773A (en) | 1986-11-25 | 1990-10-30 | Alcon Laboratories, Inc. | Topical ophthalmic compositions containing microfine retinoid particles |
| US5278151A (en) | 1987-04-02 | 1994-01-11 | Ocular Research Of Boston, Inc. | Dry eye treatment solution |
| US4914088A (en) | 1987-04-02 | 1990-04-03 | Thomas Glonek | Dry eye treatment solution and method |
| US5075104A (en) | 1989-03-31 | 1991-12-24 | Alcon Laboratories, Inc. | Ophthalmic carboxy vinyl polymer gel for dry eye syndrome |
| US5174988A (en) | 1989-07-27 | 1992-12-29 | Scientific Development & Research, Inc. | Phospholipid delivery system |
| US5583150A (en) | 1989-08-18 | 1996-12-10 | Alcon Laboratories, Inc. | 5-methyl-isoxazole-4-carboxylic acid anilides and 2-hydroxyethylidene-cyano acetic anilides for the treatment of ocular diseases |
| US5041434A (en) | 1991-08-17 | 1991-08-20 | Virginia Lubkin | Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application |
| ZA912797B (en) | 1990-05-29 | 1992-12-30 | Boston Ocular Res | Dry eye treatment process and solution |
| ES2084722T3 (es) | 1990-05-29 | 1996-05-16 | Boston Ocular Res | Composicion para tratamiento del ojo seco. |
| ATE141502T1 (de) | 1991-01-15 | 1996-09-15 | Alcon Lab Inc | Verwendung von karrageenan in topischen ophthalmologischen zusammensetzungen |
| ZA927277B (en) | 1991-10-02 | 1993-05-19 | Boston Ocular Res | Dry eye treatment process and solution. |
| US6107289A (en) | 1992-04-21 | 2000-08-22 | The Schepens Eye Research Institute, Inc. | Ocular therapy in keratoconjunctivitis sicca using topically applied androgens or TGF-β |
| US5958912A (en) | 1992-04-21 | 1999-09-28 | The Schepens Eye Research Institute, Inc. | Ocular therapy in keratoconjunctivitis sicca using topically applied androgens of TGF-β |
| ATE185697T1 (de) | 1992-04-21 | 1999-11-15 | Schepens Eye Res Inst | Androgentherapie am auge beim sjögrensyndrom |
| US5290572A (en) | 1992-08-06 | 1994-03-01 | Deo Corporation | Opthalmic composition for treating dry eye |
| US5474979A (en) | 1994-05-17 | 1995-12-12 | Allergan, Inc. | Nonirritating emulsions for sensitive tissue |
| US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| US6335358B1 (en) | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| US5696166A (en) | 1995-10-31 | 1997-12-09 | Yanni; John M. | Compositions containing hydroxyeicosatetraenoic acid derivatives and methods of use in treating dry eye disorders |
| WO1997020578A1 (en) | 1995-12-04 | 1997-06-12 | University Of Miami | Non-preserved topical corticosteroid for treatment of dry eye, filamentary keratitis, and delayed tear clearance |
| JPH1036289A (ja) | 1996-07-24 | 1998-02-10 | Sumitomo Pharmaceut Co Ltd | 神経細胞の変性または死滅抑制剤 |
| US6071904A (en) | 1996-12-11 | 2000-06-06 | Alcon Laboratories, Inc. | Process for manufacturing ophthalmic suspensions |
| US5800807A (en) | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
| CA2281224A1 (en) | 1997-02-15 | 1998-08-20 | Proscript, Inc. | Treatment of infarcts through inhibition of nf-kappab |
| JP2001517631A (ja) | 1997-09-25 | 2001-10-09 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 炎症疾患および自己免疫疾患を治療するためのプロテアソーム阻害剤、ユビキチン経路阻害剤、またはユビキチンプロテアソーム経路を介したＮＦ−κＢの活性化に干渉する剤 |
| CA2219867A1 (en) | 1997-10-31 | 1999-04-30 | Jiangping Wu | The use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock |
| WO2000003705A1 (en) | 1998-07-14 | 2000-01-27 | Alcon Laboratories, Inc. | Use of 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid for the manufacture of a medicament for treating non-allergic ophthalmic inflammatory disorders and for the prevention of ocular neovascularization |
| US6096733A (en) | 1998-12-10 | 2000-08-01 | Virginia Lubkin | Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application |
| EP1166781A4 (en) | 1999-01-20 | 2002-08-21 | Kyowa Hakko Kogyo Kk | proteasome |
| US6254860B1 (en) | 1999-04-13 | 2001-07-03 | Allergan Sales, Inc. | Ocular treatment using cyclosporin-A derivatives |
| ATE270268T1 (de) | 1999-04-27 | 2004-07-15 | Novartis Pharma Gmbh | 2,4-diamino-3-hydroxycarboxylsäurederivate als proteasome inhibitoren |
-
2002
- 2002-05-17 US US10/150,191 patent/US6740674B2/en not_active Expired - Lifetime
- 2002-05-17 DE DE60218153T patent/DE60218153T2/de not_active Expired - Lifetime
- 2002-05-17 WO PCT/US2002/015775 patent/WO2002094311A1/en not_active Ceased
- 2002-05-17 JP JP2002591027A patent/JP2004530699A/ja active Pending
- 2002-05-17 CN CNA028098544A patent/CN1509183A/zh active Pending
- 2002-05-17 CA CA2447909A patent/CA2447909C/en not_active Expired - Fee Related
- 2002-05-17 EP EP02771849A patent/EP1392355B1/en not_active Expired - Lifetime
- 2002-05-17 DK DK02771849T patent/DK1392355T3/da active
- 2002-05-17 PL PL02367287A patent/PL367287A1/xx not_active Application Discontinuation
- 2002-05-17 AT AT02771849T patent/ATE353667T1/de active
- 2002-05-17 AU AU2002308760A patent/AU2002308760B2/en not_active Ceased
- 2002-05-17 BR BR0209883-0A patent/BR0209883A/pt not_active Application Discontinuation
- 2002-05-17 MX MXPA03010634A patent/MXPA03010634A/es active IP Right Grant
- 2002-05-17 PT PT02771849T patent/PT1392355E/pt unknown
- 2002-05-17 ES ES02771849T patent/ES2278049T3/es not_active Expired - Lifetime
-
2003
- 2003-11-11 ZA ZA2003/08768A patent/ZA200308768B/en unknown
-
2007
- 2007-03-13 CY CY20071100343T patent/CY1107531T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1392355A1 (en) | 2004-03-03 |
| AU2002308760B2 (en) | 2006-05-11 |
| MXPA03010634A (es) | 2004-03-09 |
| DK1392355T3 (da) | 2007-04-30 |
| DE60218153D1 (de) | 2007-03-29 |
| ATE353667T1 (de) | 2007-03-15 |
| DE60218153T2 (de) | 2007-06-28 |
| CN1509183A (zh) | 2004-06-30 |
| WO2002094311A1 (en) | 2002-11-28 |
| US6740674B2 (en) | 2004-05-25 |
| CA2447909C (en) | 2011-04-05 |
| CY1107531T1 (el) | 2013-03-13 |
| BR0209883A (pt) | 2004-06-08 |
| US20030008910A1 (en) | 2003-01-09 |
| ZA200308768B (en) | 2005-01-26 |
| PL367287A1 (en) | 2005-02-21 |
| EP1392355B1 (en) | 2007-02-14 |
| JP2004530699A (ja) | 2004-10-07 |
| CA2447909A1 (en) | 2002-11-28 |
| PT1392355E (pt) | 2007-03-30 |
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