RU2761457C2 - N1-(4-(5-(циклопропилметил)-1-метил-1h-пиразол-4-ил)пиридин-2-ил)циклогексан-1,4-диаминовые производные и родственные соединения в качестве ингибиторов сk1 и/или irak1 для лечения рака - Google Patents
N1-(4-(5-(циклопропилметил)-1-метил-1h-пиразол-4-ил)пиридин-2-ил)циклогексан-1,4-диаминовые производные и родственные соединения в качестве ингибиторов сk1 и/или irak1 для лечения рака Download PDFInfo
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- RU2761457C2 RU2761457C2 RU2019127038A RU2019127038A RU2761457C2 RU 2761457 C2 RU2761457 C2 RU 2761457C2 RU 2019127038 A RU2019127038 A RU 2019127038A RU 2019127038 A RU2019127038 A RU 2019127038A RU 2761457 C2 RU2761457 C2 RU 2761457C2
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762453192P | 2017-02-01 | 2017-02-01 | |
| US62/453,192 | 2017-02-01 | ||
| PCT/IL2018/050100 WO2018142393A1 (en) | 2017-02-01 | 2018-01-30 | N1 -(4-(5-(cyclopropylmethyl)-1 -methyl-1 h-pyrazol-4-yl)pyridin-2-yl)cyclohexane-1,4-diamine derivatives and related compounds as ck1 and/or iraki inhibitors for treating cancer |
Publications (3)
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| US10376511B2 (en) * | 2015-08-04 | 2019-08-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Pyrazole pyrimidine derivative and uses thereof |
| EP3749666A1 (en) * | 2018-02-08 | 2020-12-16 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Heteroaryl compounds, pharmaceutical compositions thereof, and their therapeutic use |
| WO2021000957A1 (zh) * | 2019-07-04 | 2021-01-07 | 北京国鸿生物医药科技有限公司 | 一种杂环化合物、其药物组合物及用途 |
| MX2023003170A (es) * | 2020-09-17 | 2023-03-27 | Janssen Pharmaceutica Nv | Moduladores de la caseina cinasa 1 delta. |
| WO2022232259A1 (en) * | 2021-04-28 | 2022-11-03 | Cornell University | Soluble adenylyl cyclase (sac) inhibitors and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2651405A2 (en) * | 2010-12-14 | 2013-10-23 | Electrophoretics Limited | Casein kinase 1 (ck1 ) inhibitors |
| RU2604062C2 (ru) * | 2010-07-13 | 2016-12-10 | Ф.Хоффманн-Ля Рош Аг | ПРОИЗВОДНЫЕ ПИРАЗОЛО[1,5-a]ПИРИМИДИНА И ТИЕНО[3,2-b]ПИРИМИДИНА В КАЧЕСТВЕ МОДУЛЯТОРОВ IRAK-4 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007129195A2 (en) | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
| KR101990605B1 (ko) | 2011-11-04 | 2019-06-18 | 자스코 파머수티컬스, 엘엘씨 | 아미노피리미딘 키나아제 억제제 |
| CN106232122A (zh) | 2013-09-27 | 2016-12-14 | 林伯士艾瑞斯公司 | Irak抑制剂和其用途 |
| EP3057956B1 (en) | 2013-10-18 | 2021-05-05 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
| JP6787892B2 (ja) * | 2014-11-20 | 2020-11-18 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | Ｉｒａｋインヒビターとしてのヘテロアリール化合物及びその使用 |
| WO2016149756A1 (en) * | 2015-03-23 | 2016-09-29 | The University Of Melbourne | Treatment of respiratory diseases |
| US10376511B2 (en) | 2015-08-04 | 2019-08-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Pyrazole pyrimidine derivative and uses thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2604062C2 (ru) * | 2010-07-13 | 2016-12-10 | Ф.Хоффманн-Ля Рош Аг | ПРОИЗВОДНЫЕ ПИРАЗОЛО[1,5-a]ПИРИМИДИНА И ТИЕНО[3,2-b]ПИРИМИДИНА В КАЧЕСТВЕ МОДУЛЯТОРОВ IRAK-4 |
| EP2651405A2 (en) * | 2010-12-14 | 2013-10-23 | Electrophoretics Limited | Casein kinase 1 (ck1 ) inhibitors |
Non-Patent Citations (4)
| Title |
|---|
| Birgit Schittek et al. "Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis", Molecular Cancer, 2014, Vol.13, P.1-14. * |
| https://official.academic.ru/28407/%D0%A4%D0%B0%D1%80%D0%BC%D0%B0%D1%86%D0%B5%D0%B2%D1%82%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B0%D1%8F_%D0%BA%D0%BE%D0%BC%D0%BF%D0%BE%D0%B7%D0%B8%D1%86%D0%B8%D1%8F, Wayback Internet Archive Machine, 04.12.2013. * |
| Беликов В. Г. "Фармацевтическая химия". Глава 2.6 "Связь между химической структурой, свойствами веществ и их действием на организм". - М.: МЕДпресс-информ, 2007, С. 27-29. * |
| Беликов В. Г. "Фармацевтическая химия". Глава 2.6 "Связь между химической структурой, свойствами веществ и их действием на организм". - М.: МЕДпресс-информ, 2007, С. 27-29. Birgit Schittek et al. "Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis", Molecular Cancer, 2014, Vol.13, P.1-14. https://official.academic.ru/28407/%D0%A4%D0%B0%D1%80%D0%BC%D0%B0%D1%86%D0%B5%D0%B2%D1%82%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B0%D1%8F_%D0%BA%D0%BE%D0%BC%D0%BF%D0%BE%D0%B7%D0%B8%D1%86%D0%B8%D1%8F, Wayback Internet Archive Machine, 04.12.2013. * |
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| JP2020505468A (ja) | 2020-02-20 |
| ES2902885T8 (es) | 2022-04-06 |
| EP3577108B1 (en) | 2021-10-20 |
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| MX2019009083A (es) | 2019-09-10 |
| ES2902885T3 (es) | 2022-03-30 |
| EP3577108A1 (en) | 2019-12-11 |
| TW201837027A (zh) | 2018-10-16 |
| CN110475771B (zh) | 2022-09-02 |
| WO2018142393A1 (en) | 2018-08-09 |
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