JP7324836B2 - Ｊａｋ阻害剤としてのジメチルアミノアゼチジンアミド - Google Patents
Ｊａｋ阻害剤としてのジメチルアミノアゼチジンアミド Download PDFInfo
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- JP7324836B2 JP7324836B2 JP2021512257A JP2021512257A JP7324836B2 JP 7324836 B2 JP7324836 B2 JP 7324836B2 JP 2021512257 A JP2021512257 A JP 2021512257A JP 2021512257 A JP2021512257 A JP 2021512257A JP 7324836 B2 JP7324836 B2 JP 7324836B2
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- lung
- disease
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- compound
- transplant rejection
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- 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
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- 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
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- 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
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- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| PCT/US2019/049276 WO2020051105A1 (en) | 2018-09-04 | 2019-09-03 | Dimethyl amino azetidine amides as jak inhibitors |
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| UA123633C2 (uk) | 2015-11-03 | 2021-05-05 | Тереванс Байофарма Ар Енд Ді Айпі, Елелсі | Сполуки інгібітору jak-кінази для лікування респіраторного захворювання |
| WO2018165392A1 (en) | 2017-03-09 | 2018-09-13 | Theravance Biopharma R&D Ip, Llc | Jak inhibitors containing a 4-membered heterocyclic amide |
| JP2021535176A (ja) | 2018-09-04 | 2021-12-16 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｊａｋ阻害剤およびその中間体を調製するためのプロセス |
| FI3837258T3 (fi) * | 2018-09-04 | 2024-05-27 | Theravance Biopharma R&D Ip Llc | Dimetyyliaminoatsetidiiniamideja jak-estäjinä |
| UA127328C2 (uk) | 2018-09-04 | 2023-07-19 | Тереванс Байофарма Ар Енд Ді Айпі, Елелсі | 5-7-членні гетероциклічні аміди як інгібітори jak |
| 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 |
| CN115803023A (zh) * | 2020-05-08 | 2023-03-14 | 施万生物制药研发Ip有限责任公司 | 发用奈珠西替尼治疗感染冠状病毒的患者的方法 |
| WO2022271604A1 (en) | 2021-06-21 | 2022-12-29 | Theravance Biopharma R&D Ip, Llc | Method of treating a patient infected with a coronavirus and having a baseline level of crp below 150 mg/l |
| EP4359402B1 (en) * | 2021-06-25 | 2026-03-11 | Theravance Biopharma R&D IP, LLC | Imidazolo indazole compounds as jak inhibitors |
| KR20230092805A (ko) * | 2021-12-17 | 2023-06-26 | 주식회사 대웅제약 | (2R, 3S)-2-(3-(4,5-디클로로-1H-벤조[d]이미다졸-1-일)프로필)피페리딘-3-올의 신규한 산부가염 및 결정형 |
| US20250288561A1 (en) | 2022-05-05 | 2025-09-18 | Theravance Biopharma R&D Ip, Llc | Nezulcitinib for delivery by nebulized oral inhalation |
| WO2023230236A1 (en) | 2022-05-26 | 2023-11-30 | Theravance Biopharma R&D Ip, Llc | Process for preparing jak inhibitors and intermediates thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014522865A (ja) | 2011-07-27 | 2014-09-08 | ファイザー・リミテッド | インダゾール |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| EP1648455A4 (en) | 2003-07-23 | 2009-03-04 | Exelixis Inc | MODULATORS OF ALK PROTEIN (ANAPLASTIC LYMPHOMA KINASE) AND METHODS OF USE |
| 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 |
| WO2010114971A1 (en) | 2009-04-03 | 2010-10-07 | Sepracor Inc. | Compounds for treating disorders mediated by metabotropic glutamate receptor 5, and methods of use thereof |
| LT3001903T (lt) | 2009-12-21 | 2018-01-10 | Samumed, Llc | 1h-pirazolo[3,4-b]piridinai ir jų terapinis panaudojimas |
| SI3077395T1 (en) | 2013-12-05 | 2018-03-30 | Pfizer Inc. | Pyrrolo(2,3-d)pyrimidinyl, pyrrolo(2,3-b)pyrazinyl and pyrrolo(2,3-d)pyridinyl acrylamides |
| KR20170002623A (ko) | 2014-05-14 | 2017-01-06 | 화이자 인코포레이티드 | 피라졸로피리딘 및 피라졸로피리미딘 |
| 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 |
| DK3371185T3 (da) | 2015-11-03 | 2020-11-30 | Topivert Pharma Ltd | 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridin og 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepinderivater som janus-kinase-inhibitorer |
| WO2017077283A1 (en) | 2015-11-03 | 2017-05-11 | 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 |
| UA123633C2 (uk) * | 2015-11-03 | 2021-05-05 | Тереванс Байофарма Ар Енд Ді Айпі, Елелсі | Сполуки інгібітору jak-кінази для лікування респіраторного захворювання |
| WO2018165392A1 (en) | 2017-03-09 | 2018-09-13 | Theravance Biopharma R&D Ip, Llc | Jak inhibitors containing a 4-membered heterocyclic amide |
| US20180258546A1 (en) | 2017-03-09 | 2018-09-13 | Lam Research Corporation | Electroplating apparatus and methods utilizing independent control of impinging electrolyte |
| KR20200003121A (ko) | 2017-05-01 | 2020-01-08 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 저해제 화합물의 결정형 |
| WO2018204233A1 (en) | 2017-05-01 | 2018-11-08 | 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 |
| CN112566713A (zh) | 2018-07-20 | 2021-03-26 | 波里费拉公司 | 具有再循环回路的渗透模块 |
| UA127328C2 (uk) | 2018-09-04 | 2023-07-19 | Тереванс Байофарма Ар Енд Ді Айпі, Елелсі | 5-7-членні гетероциклічні аміди як інгібітори jak |
| FI3837258T3 (fi) | 2018-09-04 | 2024-05-27 | Theravance Biopharma R&D Ip Llc | Dimetyyliaminoatsetidiiniamideja jak-estäjinä |
| JP2021535176A (ja) | 2018-09-04 | 2021-12-16 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｊａｋ阻害剤およびその中間体を調製するためのプロセス |
| KR20210084512A (ko) | 2018-10-29 | 2021-07-07 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 억제제로서 2-아자비시클로 헥산 화합물 |
| HUE067145T2 (hu) | 2019-02-25 | 2024-10-28 | Henan Medinno Pharmaceutical Tech Co Ltd | JAK inhibitor vegyület és alkalmazása |
| WO2020181034A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Jak1 pathway inhibitors for the treatment of chronic lung allograft dysfunction |
| CN112279848A (zh) | 2019-07-25 | 2021-01-29 | 四川海思科制药有限公司 | 一种泛JAKs抑制剂及其用途 |
| 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 |
| CN115803023A (zh) | 2020-05-08 | 2023-03-14 | 施万生物制药研发Ip有限责任公司 | 发用奈珠西替尼治疗感染冠状病毒的患者的方法 |
| WO2022178215A1 (en) | 2021-02-19 | 2022-08-25 | Theravance Biopharma R&D Ip, Llc | Amino amide tetrahydro imidazo pyridines as jak inhibitors |
| WO2022204473A1 (en) | 2021-03-26 | 2022-09-29 | Theravance Biopharma R&D Ip, Llc | Crystalline form of a dihydrochloride salt of a jak inhibitor compound |
| WO2022271604A1 (en) * | 2021-06-21 | 2022-12-29 | Theravance Biopharma R&D Ip, Llc | Method of treating a patient infected with a coronavirus and having a baseline level of crp below 150 mg/l |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014522865A (ja) | 2011-07-27 | 2014-09-08 | ファイザー・リミテッド | インダゾール |
Non-Patent Citations (1)
| Title |
|---|
| JONES, P et al.，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，2017年，Vol.60, No.2，pp.767-786 |
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