EA037261B1 - Ингибиторы jak, содержащие 4-членный гетероциклический амид - Google Patents
Ингибиторы jak, содержащие 4-членный гетероциклический амид Download PDFInfo
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- EA037261B1 EA037261B1 EA201992126A EA201992126A EA037261B1 EA 037261 B1 EA037261 B1 EA 037261B1 EA 201992126 A EA201992126 A EA 201992126A EA 201992126 A EA201992126 A EA 201992126A EA 037261 B1 EA037261 B1 EA 037261B1
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- Eurasian Patent Office
- Prior art keywords
- lung
- compound
- disease
- pneumonia
- acute
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762469073P | 2017-03-09 | 2017-03-09 | |
| PCT/US2018/021489 WO2018165392A1 (en) | 2017-03-09 | 2018-03-08 | Jak inhibitors containing a 4-membered heterocyclic amide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201992126A1 EA201992126A1 (ru) | 2020-02-05 |
| EA037261B1 true EA037261B1 (ru) | 2021-03-01 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| EA201992126A EA037261B1 (ru) | 2017-03-09 | 2018-03-08 | Ингибиторы jak, содержащие 4-членный гетероциклический амид |
| EA201992128A EA037748B1 (ru) | 2017-03-09 | 2018-03-08 | Конденсированные имидазо-пиперидиновые ингибиторы jak |
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| Application Number | Title | Priority Date | Filing Date |
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| EA201992128A EA037748B1 (ru) | 2017-03-09 | 2018-03-08 | Конденсированные имидазо-пиперидиновые ингибиторы jak |
Country Status (20)
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|---|---|
| US (10) | US10196393B2 (https=) |
| EP (2) | EP3592743A1 (https=) |
| JP (2) | JP7134990B2 (https=) |
| KR (2) | KR102533646B1 (https=) |
| CN (2) | CN110382498B (https=) |
| AR (2) | AR111242A1 (https=) |
| AU (2) | AU2018231035B2 (https=) |
| BR (2) | BR112019018648A2 (https=) |
| CA (1) | CA2997772A1 (https=) |
| DK (1) | DK3592742T3 (https=) |
| EA (2) | EA037261B1 (https=) |
| ES (1) | ES2882186T3 (https=) |
| IL (2) | IL268679B (https=) |
| MX (2) | MX388749B (https=) |
| PH (2) | PH12019501941A1 (https=) |
| PT (1) | PT3592742T (https=) |
| SG (2) | SG11201907544VA (https=) |
| TW (2) | TWI779016B (https=) |
| WO (2) | WO2018165395A1 (https=) |
| ZA (2) | ZA201905585B (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HK1252685A1 (zh) | 2015-11-03 | 2019-05-31 | Theravance Biopharma R&D Ip, Llc | 用於治疗呼吸疾病的jak激酶抑制剂化合物 |
| US10556901B2 (en) * | 2015-11-03 | 2020-02-11 | Topivert Pharma Limited | 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine and 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepine derivatives as Janus kinase inhibitors |
| BR112019018648A2 (pt) | 2017-03-09 | 2020-06-16 | Theravance Biopharma R&D Ip, Llc | Inibidores de jak contendo uma amida heterocíclica com 4 membros |
| AR111495A1 (es) | 2017-05-01 | 2019-07-17 | Theravance Biopharma R&D Ip Llc | Compuestos de imidazo-piperidina fusionada como inhibidores de jak |
| US10406148B2 (en) | 2017-05-01 | 2019-09-10 | Theravance Biopharma R&D Ip, Llc | Methods of treatment using a JAK inhibitor compound |
| PT3837258T (pt) | 2018-09-04 | 2024-06-20 | Theravance Biopharma R&D Ip Llc | Amidas de dimetil amino azetidina como inibidores de jak |
| WO2020051139A1 (en) * | 2018-09-04 | 2020-03-12 | Theravance Biopharma R&D Ip, Llc | 5 to 7 membered heterocyclic amides as jak inhibitors |
| CA3108848A1 (en) | 2018-09-04 | 2020-03-12 | Theravance Biopharma R&D Ip, Llc | Process for preparing jak inhibitors and intermediates thereof |
| MX2021004582A (es) | 2018-10-29 | 2021-06-15 | Theravance Biopharma R&D Ip Llc | Compuesto 2-azabiciclo hexano inhibidor de jak. |
| FI3932919T3 (fi) | 2019-02-25 | 2024-08-30 | Henan Medinno Pharmaceutical Tech Co Ltd | Jak-inhibiittoriyhdiste ja sen käyttö |
| MA55201A (fr) | 2019-03-05 | 2022-01-12 | Incyte Corp | Inhibiteurs de la voie jak1 pour le traitement d'un dysfonctionnement chronique de l'allogreffe pulmonaire |
| CN114901659A (zh) * | 2019-11-26 | 2022-08-12 | 施万生物制药研发Ip有限责任公司 | 作为jak抑制剂的稠合嘧啶吡啶酮化合物 |
| WO2021136345A1 (zh) * | 2019-12-30 | 2021-07-08 | 路良 | Jak抑制剂化合物及其用途 |
| TW202144343A (zh) * | 2020-03-02 | 2021-12-01 | 美商施萬生物製藥研發 Ip有限責任公司 | Jak抑制劑化合物之結晶水合物 |
| EP3944859A1 (en) | 2020-07-30 | 2022-02-02 | Assistance Publique Hôpitaux de Paris | Method for treating immune toxicities induced by immune checkpoint inhibitors |
| WO2022178215A1 (en) * | 2021-02-19 | 2022-08-25 | Theravance Biopharma R&D Ip, Llc | Amino amide tetrahydro imidazo pyridines as jak inhibitors |
| 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 |
| JP7644873B2 (ja) * | 2021-12-17 | 2025-03-12 | デウン ファーマシューティカル カンパニー リミテッド | （２Ｒ，３Ｓ）－２－（３－（４，５－ジクロロ－１Ｈ－ベンゾ［ｄ］イミダゾール－１－イル）プロピル）ピペリジン－３－オールの新規な酸付加塩および結晶形 |
| CN117658852B (zh) * | 2023-11-15 | 2026-03-24 | 西北工业大学 | 取代苯氧乙酰肼类化合物及其制备方法和作为stat3的抗炎抑制剂的应用 |
| WO2025157904A1 (en) * | 2024-01-24 | 2025-07-31 | Kiox Pharmaceuticals Aps | Inhalable formulations of ruxolitinib, methods of manufacture and uses thereof |
| CN118903009B (zh) * | 2024-10-11 | 2025-01-21 | 江苏长泰药业股份有限公司 | 一种调节呼吸道微生态的丙酮酸钠气雾剂及其制备方法和应用 |
Citations (1)
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|---|---|---|---|---|
| WO2013014567A1 (en) * | 2011-07-27 | 2013-01-31 | Pfizer Limited | Indazoles |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| JP4836788B2 (ja) | 2003-07-23 | 2011-12-14 | エグゼリクシス， インコーポレイテッド | 未分化リンパ腫キナーゼ変調因子及びその使用法 |
| US20050090529A1 (en) | 2003-07-31 | 2005-04-28 | Pfizer Inc | 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
| US7884109B2 (en) | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
| US8648069B2 (en) | 2007-06-08 | 2014-02-11 | Abbvie Inc. | 5-substituted indazoles as kinase inhibitors |
| JP2010111624A (ja) | 2008-11-06 | 2010-05-20 | Shionogi & Co Ltd | Ｔｔｋ阻害作用を有するインダゾール誘導体 |
| EP2414340A1 (en) | 2009-04-03 | 2012-02-08 | Dainippon Sumitomo Pharma Co., Ltd. | Compounds for treating disorders mediated by metabotropic glutamate receptor 5, and methods of use thereof |
| EP2515655B1 (en) | 2009-12-21 | 2015-08-05 | Samumed, LLC | 1h-pyrazolo[3,4-beta]pyridines and therapeutic uses thereof |
| EP2338888A1 (en) | 2009-12-24 | 2011-06-29 | Almirall, S.A. | Imidazopyridine derivatives as JAK inhibitors |
| EP2771340B1 (en) | 2011-10-25 | 2016-04-13 | Sanofi | 6-(4-hydroxy-phenyl)-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| MX368464B (es) | 2013-12-05 | 2019-10-02 | Pfizer | Acrilamidas de pirrolo[2,3-d]pirimidinilo, pirrolo[2,3-b]pirazinil o y pirrolo[2,3-d]piridinilo. |
| CR20160525A (es) | 2014-05-14 | 2016-12-20 | Pfizer | Pirazolopiridinas y pirazolopirimidinas |
| WO2016026078A1 (en) | 2014-08-19 | 2016-02-25 | Changzhou Jiekai Pharmatech Co., Ltd. | Heterocyclic compounds as erk inhibitors |
| KR101663277B1 (ko) | 2015-03-30 | 2016-10-06 | 주식회사 녹십자 | TNIK, IKKε 및 TBK1 억제제로서의 피라졸계 유도체 및 이를 포함하는 약학적 조성물 |
| EP3712152B1 (en) | 2015-11-03 | 2021-01-13 | Topivert Pharma Limited | 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridine and 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepine derivatives as janus kinase inhibitors |
| HK1252685A1 (zh) | 2015-11-03 | 2019-05-31 | Theravance Biopharma R&D Ip, Llc | 用於治疗呼吸疾病的jak激酶抑制剂化合物 |
| US10556901B2 (en) | 2015-11-03 | 2020-02-11 | Topivert Pharma Limited | 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine and 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepine derivatives as Janus kinase inhibitors |
| BR112019018648A2 (pt) | 2017-03-09 | 2020-06-16 | Theravance Biopharma R&D Ip, Llc | Inibidores de jak contendo uma amida heterocíclica com 4 membros |
| US10406148B2 (en) | 2017-05-01 | 2019-09-10 | 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 |
| CN110603255B (zh) | 2017-05-01 | 2023-02-10 | 施万生物制药研发Ip有限责任公司 | Jak抑制剂化合物的结晶型式 |
| KR102032418B1 (ko) | 2017-06-15 | 2019-10-16 | 한국화학연구원 | 접합 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 브루톤티로신 키나제 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |
| WO2020051139A1 (en) | 2018-09-04 | 2020-03-12 | Theravance Biopharma R&D Ip, Llc | 5 to 7 membered heterocyclic amides as jak inhibitors |
| CA3108848A1 (en) | 2018-09-04 | 2020-03-12 | Theravance Biopharma R&D Ip, Llc | Process for preparing jak inhibitors and intermediates thereof |
| PT3837258T (pt) | 2018-09-04 | 2024-06-20 | Theravance Biopharma R&D Ip Llc | Amidas de dimetil amino azetidina como inibidores de jak |
-
2018
- 2018-03-08 BR BR112019018648-4A patent/BR112019018648A2/pt not_active IP Right Cessation
- 2018-03-08 TW TW107107936A patent/TWI779016B/zh not_active IP Right Cessation
- 2018-03-08 AR ARP180100543A patent/AR111242A1/es unknown
- 2018-03-08 CN CN201880016693.XA patent/CN110382498B/zh not_active Expired - Fee Related
- 2018-03-08 DK DK18711796.5T patent/DK3592742T3/da active
- 2018-03-08 WO PCT/US2018/021492 patent/WO2018165395A1/en not_active Ceased
- 2018-03-08 WO PCT/US2018/021489 patent/WO2018165392A1/en not_active Ceased
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- 2018-03-08 SG SG11201907544VA patent/SG11201907544VA/en unknown
- 2018-03-08 AU AU2018231035A patent/AU2018231035B2/en not_active Ceased
- 2018-03-08 TW TW107107939A patent/TWI754019B/zh not_active IP Right Cessation
- 2018-03-08 JP JP2019548369A patent/JP7134990B2/ja active Active
- 2018-03-08 MX MX2019010539A patent/MX388749B/es unknown
- 2018-03-08 EP EP18712398.9A patent/EP3592743A1/en not_active Withdrawn
- 2018-03-08 AR ARP180100542A patent/AR111241A1/es not_active Application Discontinuation
- 2018-03-08 KR KR1020197029543A patent/KR102533646B1/ko active Active
- 2018-03-08 SG SG11201907840RA patent/SG11201907840RA/en unknown
- 2018-03-08 PT PT187117965T patent/PT3592742T/pt unknown
- 2018-03-08 CA CA2997772A patent/CA2997772A1/en active Pending
- 2018-03-08 EA EA201992126A patent/EA037261B1/ru not_active IP Right Cessation
- 2018-03-08 EP EP18711796.5A patent/EP3592742B1/en active Active
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- 2018-03-08 US US15/915,418 patent/US10196393B2/en active Active
- 2018-03-08 KR KR1020197029560A patent/KR102526764B1/ko active Active
- 2018-03-08 MX MX2019010541A patent/MX388750B/es unknown
- 2018-03-08 CN CN201880017046.0A patent/CN110461839B/zh active Active
- 2018-03-08 JP JP2019548449A patent/JP6974487B2/ja active Active
- 2018-03-08 AU AU2018231032A patent/AU2018231032B2/en not_active Ceased
- 2018-03-08 US US15/915,434 patent/US10208040B2/en active Active
- 2018-03-08 EA EA201992128A patent/EA037748B1/ru unknown
- 2018-12-17 US US16/222,647 patent/US10392386B2/en active Active
- 2018-12-19 US US16/225,473 patent/US10519153B2/en active Active
-
2019
- 2019-07-15 US US16/511,410 patent/US10550118B2/en active Active
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013014567A1 (en) * | 2011-07-27 | 2013-01-31 | Pfizer Limited | Indazoles |
Non-Patent Citations (1)
| Title |
|---|
| PETER JONES, R. IAN STORER, YOGESH A. SABNIS, FLORIAN M. WAKENHUT, GAVIN A. WHITLOCK, KATHERINE S. ENGLAND, TAKASUKE MUKAIYAMA, CH: "Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 60, no. 2, 26 January 2017 (2017-01-26), US, pages 767 - 786, XP055468539, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01634 * |
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