RU2652795C2 - Производные 2-фенил-оксазол-4-карбоксамида, модулирующие активность jak и tyk2 киназ - Google Patents
Производные 2-фенил-оксазол-4-карбоксамида, модулирующие активность jak и tyk2 киназ Download PDFInfo
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- RU2652795C2 RU2652795C2 RU2016111522A RU2016111522A RU2652795C2 RU 2652795 C2 RU2652795 C2 RU 2652795C2 RU 2016111522 A RU2016111522 A RU 2016111522A RU 2016111522 A RU2016111522 A RU 2016111522A RU 2652795 C2 RU2652795 C2 RU 2652795C2
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- alkyl
- compound
- disease
- optionally substituted
- oxazole
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Classifications
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| PCT/EP2013/068198 WO2015032423A1 (en) | 2013-09-03 | 2013-09-03 | Pharmaceutical compounds |
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| RU2016111522A RU2016111522A (ru) | 2017-10-09 |
| RU2652795C2 true RU2652795C2 (ru) | 2018-05-03 |
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| JP (1) | JP6239118B2 (ko) |
| KR (1) | KR102191084B1 (ko) |
| CN (1) | CN105793245B (ko) |
| AU (1) | AU2013399913B2 (ko) |
| BR (1) | BR112016004723B1 (ko) |
| CA (1) | CA2941824C (ko) |
| IL (1) | IL244380B (ko) |
| MX (1) | MX369974B (ko) |
| RU (1) | RU2652795C2 (ko) |
| SG (1) | SG11201601503SA (ko) |
| WO (1) | WO2015032423A1 (ko) |
| ZA (1) | ZA201602047B (ko) |
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| GB201617871D0 (en) | 2016-10-21 | 2016-12-07 | Sareum Limited | Pharmaceutical compounds |
| WO2019132654A1 (en) * | 2017-12-27 | 2019-07-04 | Erasmus University Medical Center Rotterdam | Methods of treating sarcoidosis |
| WO2020009566A1 (en) * | 2018-07-04 | 2020-01-09 | Erasmus University Medical Center Rotterdam | Methods of treating sarcoidosis |
| GB201816369D0 (en) | 2018-10-08 | 2018-11-28 | Sareum Ltd | Pharmaceutical compounds |
| AU2019443366A1 (en) | 2019-04-30 | 2021-12-02 | Celgene Corporation | Combination therapies comprising apremilast and Tyk2 inhibitors |
| GB202005114D0 (en) | 2020-04-07 | 2020-05-20 | Sareum Ltd | Crystalline Forms of a Pharmaceutical Compound |
| EP3944859A1 (en) | 2020-07-30 | 2022-02-02 | Assistance Publique Hôpitaux de Paris | Method for treating immune toxicities induced by immune checkpoint inhibitors |
| WO2023055901A2 (en) | 2021-09-30 | 2023-04-06 | Bristol-Myers Squibb Company | Methods for determining responsiveness to tyk2 inhibitors |
| WO2023076161A1 (en) | 2021-10-25 | 2023-05-04 | Kymera Therapeutics, Inc. | Tyk2 degraders and uses thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU623518A3 (ru) * | 1973-12-17 | 1978-09-05 | "Лилли Индастриз Лимитед" (Фирма) | Способ получени производных оксазола |
| WO2008139161A1 (en) * | 2007-05-10 | 2008-11-20 | Sareum Limited | Oxazole tyrosine kinase inhibitors |
| WO2010055304A2 (en) * | 2008-11-13 | 2010-05-20 | Sareum Limited | Pharmaceutical compounds |
| RU2011114992A (ru) * | 2008-09-18 | 2012-10-27 | Домпе С.П.А. (It) | 2-арилпропионовые кислоты и производные, и фармацевтические композиции, содержащие указанные соединения |
| WO2013055645A1 (en) * | 2011-10-12 | 2013-04-18 | Array Biopharma Inc. | 5,7-substituted-imidazo[1,2-c]pyrimidines |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100404256B1 (ko) * | 1998-05-05 | 2003-11-01 | 에프. 호프만-라 로슈 아게 | 피-38 엠에이피 키나제 저해제로서의 피라졸 유도체 |
| AU2008266883B2 (en) | 2007-06-20 | 2014-01-30 | Merck Sharp & Dohme Corp. | Inhibitors of janus kinases |
| US8278335B2 (en) | 2008-04-21 | 2012-10-02 | Merck Sharp & Dohme Corp. | Inhibitors of Janus kinases |
| CA2727928A1 (en) | 2008-06-18 | 2009-12-23 | Merck Sharp & Dohme Corp. | Inhibitors of janus kinases |
| JP2011527680A (ja) | 2008-07-09 | 2011-11-04 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｊａｎｕｓキナーゼの阻害剤 |
| US20130096104A1 (en) | 2010-03-17 | 2013-04-18 | Genentech, Inc. | Imidazopyridine compounds, compositions and methods of use |
| WO2012000970A1 (en) | 2010-07-01 | 2012-01-05 | Cellzome Limited | Triazolopyridines as tyk2 inhibitors |
| US20130231340A1 (en) * | 2012-03-02 | 2013-09-05 | Sareum Limited | Pharmaceutical compounds |
-
2013
- 2013-09-03 CN CN201380080517.XA patent/CN105793245B/zh active Active
- 2013-09-03 SG SG11201601503SA patent/SG11201601503SA/en unknown
- 2013-09-03 RU RU2016111522A patent/RU2652795C2/ru active
- 2013-09-03 AU AU2013399913A patent/AU2013399913B2/en active Active
- 2013-09-03 MX MX2016002738A patent/MX369974B/es active IP Right Grant
- 2013-09-03 KR KR1020167007925A patent/KR102191084B1/ko active IP Right Grant
- 2013-09-03 JP JP2016537144A patent/JP6239118B2/ja active Active
- 2013-09-03 CA CA2941824A patent/CA2941824C/en active Active
- 2013-09-03 BR BR112016004723-0A patent/BR112016004723B1/pt active IP Right Grant
- 2013-09-03 WO PCT/EP2013/068198 patent/WO2015032423A1/en active Application Filing
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2016
- 2016-03-02 IL IL244380A patent/IL244380B/en active IP Right Grant
- 2016-03-29 ZA ZA2016/02047A patent/ZA201602047B/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU623518A3 (ru) * | 1973-12-17 | 1978-09-05 | "Лилли Индастриз Лимитед" (Фирма) | Способ получени производных оксазола |
| WO2008139161A1 (en) * | 2007-05-10 | 2008-11-20 | Sareum Limited | Oxazole tyrosine kinase inhibitors |
| RU2011114992A (ru) * | 2008-09-18 | 2012-10-27 | Домпе С.П.А. (It) | 2-арилпропионовые кислоты и производные, и фармацевтические композиции, содержащие указанные соединения |
| WO2010055304A2 (en) * | 2008-11-13 | 2010-05-20 | Sareum Limited | Pharmaceutical compounds |
| WO2013055645A1 (en) * | 2011-10-12 | 2013-04-18 | Array Biopharma Inc. | 5,7-substituted-imidazo[1,2-c]pyrimidines |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20160048883A (ko) | 2016-05-04 |
| BR112016004723A2 (ko) | 2017-08-01 |
| ZA201602047B (en) | 2020-12-23 |
| CA2941824A1 (en) | 2015-03-12 |
| MX2016002738A (es) | 2016-08-11 |
| AU2013399913A1 (en) | 2016-03-24 |
| IL244380A0 (en) | 2016-04-21 |
| AU2013399913B2 (en) | 2018-03-15 |
| SG11201601503SA (en) | 2016-03-30 |
| KR102191084B1 (ko) | 2020-12-15 |
| BR112016004723B1 (pt) | 2022-08-30 |
| WO2015032423A1 (en) | 2015-03-12 |
| RU2016111522A (ru) | 2017-10-09 |
| JP2016529264A (ja) | 2016-09-23 |
| IL244380B (en) | 2018-01-31 |
| CN105793245B (zh) | 2018-03-20 |
| CA2941824C (en) | 2020-08-25 |
| JP6239118B2 (ja) | 2017-11-29 |
| CN105793245A (zh) | 2016-07-20 |
| MX369974B (es) | 2019-11-27 |
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