CN114007621A - 用于治疗慢性肺同种异体移植物功能障碍的jak1途径抑制剂 - Google Patents
用于治疗慢性肺同种异体移植物功能障碍的jak1途径抑制剂 Download PDFInfo
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- CN114007621A CN114007621A CN202080024215.0A CN202080024215A CN114007621A CN 114007621 A CN114007621 A CN 114007621A CN 202080024215 A CN202080024215 A CN 202080024215A CN 114007621 A CN114007621 A CN 114007621A
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Classifications
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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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (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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- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US62/814,085 | 2019-03-05 | ||
| PCT/US2020/021088 WO2020181034A1 (en) | 2019-03-05 | 2020-03-05 | Jak1 pathway inhibitors for the treatment of chronic lung allograft dysfunction |
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| CN114007621A true CN114007621A (zh) | 2022-02-01 |
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| EA (1) | EA202192426A1 (enExample) |
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| UA (1) | UA130579C2 (enExample) |
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Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
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| BR112021004063A2 (pt) | 2018-09-04 | 2021-05-25 | Theravance Biopharma R&D Ip, Llc | amidas heterocíclicas com 5 a 7 membros como inibidores de jak |
| DK3837258T3 (da) | 2018-09-04 | 2024-07-22 | Theravance Biopharma R&D Ip Llc | Dimethyl amino azetidine amides as jak inhibitors |
| EP3853229A1 (en) | 2018-10-29 | 2021-07-28 | Theravance Biopharma R&D IP, LLC | 2-azabicyclo hexane compound as jak inhibitor |
| KR20210109522A (ko) | 2018-10-31 | 2021-09-06 | 인사이트 코포레이션 | 혈액 질환의 치료를 위한 병용 요법 |
| UA130579C2 (uk) * | 2019-03-05 | 2026-03-25 | Інсайт Корпорейшн | Інгібітори шляхів jak1 для лікування хронічної дисфункції алотрансплантата легень |
| US11992490B2 (en) | 2019-10-16 | 2024-05-28 | Incyte Corporation | Use of JAK1 inhibitors for the treatment of cutaneous lupus erythematosus and Lichen planus (LP) |
| KR20220149585A (ko) | 2020-03-02 | 2022-11-08 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 억제제 화합물의 결정성 수화물 |
| CN117120055A (zh) * | 2021-01-11 | 2023-11-24 | 因赛特公司 | 包含jak通路抑制剂和rock抑制剂的组合疗法 |
| CA3207859A1 (en) * | 2021-01-11 | 2022-07-14 | Incyte Corporation | Combination therapy comprising jak pathway inhibitor and rock inhibitor |
| TW202317550A (zh) | 2021-06-25 | 2023-05-01 | 美商施萬生物製藥研發 Ip有限責任公司 | 作為jak抑制劑之咪唑吲唑化合物 |
| KR102952944B1 (ko) | 2021-10-15 | 2026-04-14 | 주식회사 엘지에너지솔루션 | 용접봉 체결 방법 및 이에 의해 용접봉이 수직으로 체결된 용접 장치 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150118229A1 (en) * | 2013-10-24 | 2015-04-30 | Abbvie Inc. | Jak1 selective inhibitor and uses thereof |
| CN105294699A (zh) * | 2015-12-04 | 2016-02-03 | 上海勋和医药科技有限公司 | 巴瑞替尼的制备方法 |
| CN105579032A (zh) * | 2013-08-07 | 2016-05-11 | 因赛特公司 | Jak1抑制剂的持续释放剂型 |
| CN106456773A (zh) * | 2014-02-28 | 2017-02-22 | 因赛特公司 | 用于治疗骨髓增生异常综合征的jak1抑制剂 |
| WO2018099680A1 (en) * | 2016-11-29 | 2018-06-07 | Sandoz Ag | Citrate salts of a janus kinase (jak) inhibitor |
| CN108366994A (zh) * | 2016-10-03 | 2018-08-03 | 梁从新 | 新型Jak1选择性抑制剂及其用途 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1294358B1 (en) | 2000-06-28 | 2004-08-18 | Smithkline Beecham Plc | Wet milling process |
| HUE028588T2 (hu) | 2005-12-13 | 2016-12-28 | Incyte Holdings Corp | Heteroaril-szubsztituált pirrolo[2,3-b]piridinek és pirrolo[2,3-b]pirimidinek mint Janus-kináz inhibitorok |
| EP2001881A2 (en) | 2006-03-07 | 2008-12-17 | Endacea, Inc. | Compositions and methods for treating respiratory disorders |
| US8058227B2 (en) | 2006-10-03 | 2011-11-15 | Medical University Of South Carolina | Method of treating fibrosis in a subject in need thereof comprising administering a composition comprising a CSD |
| EP2740731B1 (en) | 2007-06-13 | 2016-03-23 | Incyte Holdings Corporation | Crystalline salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile |
| EP2684564A1 (en) | 2008-04-17 | 2014-01-15 | Sanofi | Use of dronedarone for the preparation of a medicament for use in the prevention of cardiovascular hospitalization or in the prevention of atrial fibrillation |
| NZ596479A (en) | 2009-05-22 | 2014-01-31 | Incyte Corp | N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| TW201113285A (en) | 2009-09-01 | 2011-04-16 | Incyte Corp | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| EP4782062A2 (en) | 2009-12-01 | 2026-07-29 | AbbVie Inc. | Novel tricyclic compounds |
| CA2792508C (en) | 2010-03-10 | 2018-01-16 | Incyte Corporation | Piperidin-4-yl azetidine derivatives as jak1 inhibitors |
| RU2013120966A (ru) | 2010-10-08 | 2014-11-20 | Эббви Инк. | ФУРО[3,2-d]ПИРИМИДИНОВЫЕ СОЕДИНЕНИЯ |
| ES2536415T3 (es) | 2010-11-19 | 2015-05-25 | Incyte Corporation | Pirrolopiridinas y pirrolopirimidinas sustituidas heterocíclicas como inhibidores de JAK |
| CA2818542A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| US8691807B2 (en) | 2011-06-20 | 2014-04-08 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| TW201406761A (zh) | 2012-05-18 | 2014-02-16 | Incyte Corp | 做爲ｊａｋ抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物 |
| EP3450434B1 (en) | 2012-06-15 | 2021-02-24 | CoNCERT Pharmaceuticals, Inc. | Deuterated derivatives of ruxolitinib |
| BR112015003153A2 (pt) | 2012-08-17 | 2017-07-04 | Concert Pharmaceuticals Inc | baricitinib deuterado |
| CA2888816A1 (en) | 2012-11-01 | 2014-05-08 | Incyte Corporation | Tricyclic fused thiophene derivatives as jak inhibitors |
| EP3489239B1 (en) | 2013-03-06 | 2021-09-15 | Incyte Holdings Corporation | Processes and intermediates for making a jak inhibitor |
| CR20190156A (es) * | 2013-05-17 | 2019-05-16 | Incyte Corp | Derivados de bipirazol como inhibidores jak |
| SG11201609016VA (en) | 2014-04-30 | 2016-11-29 | Incyte Corp | Processes of preparing a jak1 inhibitor and new forms thereto |
| WO2015184305A1 (en) * | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| TWI710560B (zh) | 2015-11-03 | 2020-11-21 | 美商施萬生物製藥研發Ｉｐ有限責任公司 | 用於治療呼吸疾病之jak激酶抑制劑化合物 |
| TWI754019B (zh) | 2017-03-09 | 2022-02-01 | 美商施萬生物製藥研發 Ip有限責任公司 | 含有4員雜環醯胺之jak抑制劑 |
| AU2018261588A1 (en) | 2017-05-01 | 2019-10-31 | Theravance Biopharma R&D Ip, Llc | Methods of treatment using a JAK inhibitor compound |
| AR111495A1 (es) | 2017-05-01 | 2019-07-17 | Theravance Biopharma R&D Ip Llc | Compuestos de imidazo-piperidina fusionada como inhibidores de jak |
| MD3746429T2 (ro) | 2018-01-30 | 2022-08-31 | Incyte Corp | Procedee pentru prepararea de (1-(3-fluoro-2-(trifluorometil)izonicotinil)piperidin-4-onă) |
| CA3091339A1 (en) | 2018-02-16 | 2019-08-22 | Incyte Corporation | Jak1 pathway inhibitors for the treatment of cytokine-related disorders |
| KR20260080448A (ko) | 2018-03-30 | 2026-06-02 | 인사이트 코포레이션 | Jak 억제제를 사용하는 화농성 한선염의 치료 |
| CN112567247A (zh) | 2018-04-13 | 2021-03-26 | 因赛特公司 | 用于移植物抗宿主病的生物标志物 |
| KR20210109522A (ko) | 2018-10-31 | 2021-09-06 | 인사이트 코포레이션 | 혈액 질환의 치료를 위한 병용 요법 |
| US11596632B2 (en) | 2018-12-19 | 2023-03-07 | Incyte Corporation | JAK1 pathway inhibitors for the treatment of gastrointestinal disease |
| UA130579C2 (uk) | 2019-03-05 | 2026-03-25 | Інсайт Корпорейшн | Інгібітори шляхів jak1 для лікування хронічної дисфункції алотрансплантата легень |
| US11624751B2 (en) | 2019-03-19 | 2023-04-11 | Incyte Corporation | Biomarkers for vitiligo |
-
2020
- 2020-03-05 UA UAA202105585A patent/UA130579C2/uk unknown
- 2020-03-05 IL IL285999A patent/IL285999B2/en unknown
- 2020-03-05 JP JP2021552624A patent/JP2022524997A/ja active Pending
- 2020-03-05 SG SG11202109563WA patent/SG11202109563WA/en unknown
- 2020-03-05 WO PCT/US2020/021088 patent/WO2020181034A1/en not_active Ceased
- 2020-03-05 KR KR1020217031644A patent/KR20210137087A/ko active Pending
- 2020-03-05 MA MA055201A patent/MA55201A/fr unknown
- 2020-03-05 AU AU2020232757A patent/AU2020232757B2/en active Active
- 2020-03-05 EA EA202192426A patent/EA202192426A1/ru unknown
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- 2020-03-05 PH PH1/2021/552130A patent/PH12021552130A1/en unknown
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105579032A (zh) * | 2013-08-07 | 2016-05-11 | 因赛特公司 | Jak1抑制剂的持续释放剂型 |
| US20150118229A1 (en) * | 2013-10-24 | 2015-04-30 | Abbvie Inc. | Jak1 selective inhibitor and uses thereof |
| CN106456773A (zh) * | 2014-02-28 | 2017-02-22 | 因赛特公司 | 用于治疗骨髓增生异常综合征的jak1抑制剂 |
| CN105294699A (zh) * | 2015-12-04 | 2016-02-03 | 上海勋和医药科技有限公司 | 巴瑞替尼的制备方法 |
| CN108366994A (zh) * | 2016-10-03 | 2018-08-03 | 梁从新 | 新型Jak1选择性抑制剂及其用途 |
| WO2018099680A1 (en) * | 2016-11-29 | 2018-06-07 | Sandoz Ag | Citrate salts of a janus kinase (jak) inhibitor |
Non-Patent Citations (1)
| Title |
|---|
| SCHOETTLER等: "Ruxolitinib is an effective steroid sparing agent in children with steroid refractory/dependent bronchiolitis obliterans syndrome after allogenic hematopoietic cell transplantation", BONE MARROW TRANSLPANTATION, vol. 54, no. 7, pages 1158, XP036825942, DOI: 10.1038/s41409-019-0450-3 * |
Also Published As
| Publication number | Publication date |
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| MX2024007081A (es) | 2024-06-21 |
| US11406640B2 (en) | 2022-08-09 |
| EP4691567A2 (en) | 2026-02-11 |
| JP2022524997A (ja) | 2022-05-11 |
| UA130579C2 (uk) | 2026-03-25 |
| AU2020232757B2 (en) | 2025-09-11 |
| SG11202109563WA (en) | 2021-09-29 |
| PH12021552130A1 (en) | 2022-08-31 |
| WO2020181034A1 (en) | 2020-09-10 |
| US20200281931A1 (en) | 2020-09-10 |
| IL285999B2 (en) | 2026-01-01 |
| EP4691567A3 (en) | 2026-04-29 |
| AU2020232757A1 (en) | 2021-10-07 |
| CA3132371A1 (en) | 2020-09-10 |
| IL285999B1 (en) | 2025-09-01 |
| KR20210137087A (ko) | 2021-11-17 |
| MA55201A (fr) | 2022-01-12 |
| MX2021010545A (es) | 2021-11-17 |
| US20220331325A1 (en) | 2022-10-20 |
| IL285999A (en) | 2021-10-31 |
| US11896595B2 (en) | 2024-02-13 |
| EP3934651A1 (en) | 2022-01-12 |
| EA202192426A1 (ru) | 2021-11-15 |
| JP2025087734A (ja) | 2025-06-10 |
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