EA038531B1 - Способ лечения амиотрофного латерального склероза, применение фармацевтической композиции, содержащей мазитиниб - Google Patents
Способ лечения амиотрофного латерального склероза, применение фармацевтической композиции, содержащей мазитиниб Download PDFInfo
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- EA038531B1 EA038531B1 EA201800499A EA201800499A EA038531B1 EA 038531 B1 EA038531 B1 EA 038531B1 EA 201800499 A EA201800499 A EA 201800499A EA 201800499 A EA201800499 A EA 201800499A EA 038531 B1 EA038531 B1 EA 038531B1
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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Landscapes
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- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16162490 | 2016-03-25 | ||
| PCT/EP2017/057134 WO2017162884A1 (en) | 2016-03-25 | 2017-03-24 | Use of masitinib for treatment of an amyotrophic lateral sclerosis patient subpopulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201800499A1 EA201800499A1 (ru) | 2019-03-29 |
| EA038531B1 true EA038531B1 (ru) | 2021-09-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201800499A EA038531B1 (ru) | 2016-03-25 | 2017-03-24 | Способ лечения амиотрофного латерального склероза, применение фармацевтической композиции, содержащей мазитиниб |
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| JP (2) | JP7250312B2 (enExample) |
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| MX (1) | MX390495B (enExample) |
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| PL (1) | PL3240538T3 (enExample) |
| PT (1) | PT3240538T (enExample) |
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| US9925282B2 (en) | 2009-01-29 | 2018-03-27 | The General Hospital Corporation | Cromolyn derivatives and related methods of imaging and treatment |
| JP6499077B2 (ja) | 2012-10-25 | 2019-04-10 | ザ ジェネラル ホスピタル コーポレイション | アルツハイマー病と関連疾患の治療のための併用療法 |
| US10525005B2 (en) | 2013-05-23 | 2020-01-07 | The General Hospital Corporation | Cromolyn compositions and methods thereof |
| CA2928028A1 (en) | 2013-10-22 | 2015-04-30 | The General Hospital Corporation | Cromolyn derivatives and related methods of imaging and treatment |
| CN116889562A (zh) * | 2016-08-31 | 2023-10-17 | 通用医疗公司 | 与神经退行性疾病相关的神经炎症中的巨噬细胞/小胶质细胞 |
| CN109073634B (zh) | 2016-11-25 | 2022-07-08 | 基诺富公司 | 用于诱导神经干细胞的分化和保护的组合物及使用该组合物诱导神经再生的方法 |
| CN110475555A (zh) * | 2017-03-28 | 2019-11-19 | 诺华股份有限公司 | 治疗多发性硬化的新方法 |
| MX2019014343A (es) * | 2017-05-30 | 2020-08-03 | Deciphera Pharmaceuticals Inc | Uso de 1-[4-bromo-5-[1-etil-7-(metilamino)-2-oxo-1,2-dihidro-1,6-n aftiridin-3-il]-2-fluorofenil]-3-fenilurea y analogos para el tratamiento de canceres asociados con anomalias geneticas en el receptor alfa del factor de crecimiento derivado de plaquetas. |
| EP3762013A4 (en) * | 2018-03-05 | 2022-05-11 | The Schepens Eye Research Institute, Inc. | THERAPY FOR GLAUCOMA AND OPTICAL NEUROPATHY BY TARGETING COLONY-STIMULATING FACTORS |
| EP3817739A4 (en) | 2018-07-02 | 2022-04-13 | The General Hospital Corporation | POWDERED FORMULATIONS OF CROMOLYN SODIUM AND ALPHA-LACTOSE |
| KR20210113610A (ko) | 2018-12-10 | 2021-09-16 | 더 제너럴 하스피탈 코포레이션 | 크로몰린 에스테르 및 이의 용도 |
| CN112618717A (zh) * | 2019-09-24 | 2021-04-09 | 北京大学深圳研究生院 | Btk抑制剂用于治疗肌萎缩侧索硬化症的用途 |
| SMT202400484T1 (it) * | 2019-12-30 | 2025-01-14 | Deciphera Pharmaceuticals Llc | Composizioni di 1-(4-bromo-5-(1-etil-7-(metilammino)-2-osso-1,2-diidro-1,6-naftiridin-3-il)-2-fluorofenil)-3-fenilurea |
| US12458622B2 (en) | 2020-04-06 | 2025-11-04 | The General Hospital Corporation | Methods of treatment of coronavirus-induced inflammation conditions |
| WO2025113494A1 (zh) * | 2023-11-27 | 2025-06-05 | 浙江径科医药有限公司 | 多环类化合物及其应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014145909A2 (en) * | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone compounds and methods of treating disorders |
| WO2015063318A1 (en) * | 2013-11-04 | 2015-05-07 | Ab Science | Use of masitinib for treatment of amyotrophic lateral sclerosis |
Family Cites Families (8)
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|---|---|---|---|---|
| TW225528B (enExample) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| US8450302B2 (en) | 2002-08-02 | 2013-05-28 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
| MXPA05001277A (es) | 2002-08-02 | 2005-10-06 | Ab Science | 2-(3-aminoaril)amino-4-aril-tiazoles y su uso como inhibidores del c-kit. |
| SI2118099T1 (sl) | 2007-02-13 | 2011-11-30 | Ab Science | Postopek za sintezo 2-aminotiazolnih spojin kot kinaznih inhibitorjev |
| TW201204360A (en) | 2010-04-20 | 2012-02-01 | Ab Science | Treatment of multiple sclerosis with MASITINIB |
| US10272082B2 (en) | 2011-07-13 | 2019-04-30 | Cytokinetics, Inc. | Combination ALS therapy |
| AU2013326463B2 (en) * | 2012-10-04 | 2018-01-18 | Ab Science | Use of masitinib for treatment of cancer in patient subpopulations identified using predictor factors |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014145909A2 (en) * | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone compounds and methods of treating disorders |
| WO2015063318A1 (en) * | 2013-11-04 | 2015-05-07 | Ab Science | Use of masitinib for treatment of amyotrophic lateral sclerosis |
Non-Patent Citations (1)
| Title |
|---|
| RYU KATSUMATA, SHINSUKE ISHIGAKI, MASAHISA KATSUNO, KAORI KAWAI, JUN SONE, ZHE HUANG, HIROAKI ADACHI, FUMIAKI TANAKA, FUMIHIKO URA: "c-Abl Inhibition Delays Motor Neuron Degeneration in the G93A Mouse, an Animal Model of Amyotrophic Lateral Sclerosis", PLOS ONE, vol. 7, no. 9, pages e46185, XP055370442, DOI: 10.1371/journal.pone.0046185 * |
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| KR20180125966A (ko) | 2018-11-26 |
| ES2899929T3 (es) | 2022-03-15 |
| CN108883108B (zh) | 2021-08-06 |
| DK3240538T3 (da) | 2021-12-06 |
| NZ745778A (en) | 2022-07-01 |
| KR102293847B1 (ko) | 2021-08-26 |
| IL261856A (en) | 2018-10-31 |
| EA201800499A1 (ru) | 2019-03-29 |
| PL3240538T3 (pl) | 2022-01-31 |
| MX2018011349A (es) | 2019-02-07 |
| US10092564B2 (en) | 2018-10-09 |
| US20180117037A1 (en) | 2018-05-03 |
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| SI3240538T1 (sl) | 2022-02-28 |
| JP2022037132A (ja) | 2022-03-08 |
| AU2017236177B2 (en) | 2022-03-31 |
| IL261856B (en) | 2022-04-01 |
| EP3240538A1 (en) | 2017-11-08 |
| EP3240538B1 (en) | 2021-09-29 |
| CA3018635C (en) | 2023-09-26 |
| PT3240538T (pt) | 2021-12-07 |
| BR112018069515A2 (pt) | 2019-04-16 |
| AU2017236177A1 (en) | 2018-09-20 |
| JP7250312B2 (ja) | 2023-04-03 |
| WO2017162884A1 (en) | 2017-09-28 |
| HUE057398T2 (hu) | 2022-05-28 |
| CA3018635A1 (en) | 2017-09-28 |
| CN108883108A (zh) | 2018-11-23 |
| JP2019515884A (ja) | 2019-06-13 |
| SG11201808106YA (en) | 2018-10-30 |
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