KR20070104641A - 단백질 키나제의 억제제로 유용한 피롤로피리미딘 - Google Patents
단백질 키나제의 억제제로 유용한 피롤로피리미딘 Download PDFInfo
- Publication number
- KR20070104641A KR20070104641A KR1020077020046A KR20077020046A KR20070104641A KR 20070104641 A KR20070104641 A KR 20070104641A KR 1020077020046 A KR1020077020046 A KR 1020077020046A KR 20077020046 A KR20077020046 A KR 20077020046A KR 20070104641 A KR20070104641 A KR 20070104641A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- aliphatic
- alkyl
- optionally substituted
- cycloaliphatic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190064555A (ko) | 2019-05-31 | 2019-06-10 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
| KR20190096917A (ko) | 2019-08-12 | 2019-08-20 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
Families Citing this family (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7884109B2 (en) | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
| WO2006127587A1 (en) * | 2005-05-20 | 2006-11-30 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
| EP2270014A1 (en) | 2005-09-22 | 2011-01-05 | Incyte Corporation | Azepine inhibitors of janus kinases |
| AU2015201850B2 (en) * | 2005-12-13 | 2017-03-02 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| UA116187C2 (uk) * | 2005-12-13 | 2018-02-26 | Інсайт Холдінгс Корпорейшн | ГЕТЕРОАРИЛЗАМІЩЕНІ ПІРОЛО[2,3-b]ПІРИДИНИ Й ПІРОЛО[2,3-b]ПІРИМІДИНИ ЯК ІНГІБІТОРИ ЯНУС-КІНАЗИ |
| TWI424999B (zh) | 2006-01-17 | 2014-02-01 | Vertex Pharma | 適合作為傑納斯激酶（ｊａｎｕｓ ｋｉｎａｓｅ）抑制劑之氮雜吲哚 |
| US7989459B2 (en) | 2006-02-17 | 2011-08-02 | Pharmacopeia, Llc | Purinones and 1H-imidazopyridinones as PKC-theta inhibitors |
| CA2648250A1 (en) * | 2006-04-05 | 2007-10-18 | Vertex Pharmaceuticals Incorporated | Deazapurines useful as inhibitors of janus kinases |
| CL2007002867A1 (es) | 2006-10-04 | 2008-06-27 | Pharmacopeia Inc | Compuestos derivados de 2-(bencimidazolil)purina, inhibidores de janus quinasa 3; composicion farmaceutica que los contiene; y su uso para tratar enfermedades autoinmune, inflamatorias, cardiovasculares, rechazo de implante, entre otras. |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| WO2008043031A1 (en) | 2006-10-04 | 2008-04-10 | Pharmacopeia, Inc. | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| AU2007338574A1 (en) | 2006-11-01 | 2008-07-03 | Vertex Pharmaceuticals Incorporated | Tricyclic heteroaryl compounds useful as inhibitors of Janus kinase |
| WO2008060301A1 (en) * | 2006-11-16 | 2008-05-22 | Pharmacopeia , Llc | 7-substituted purine derivatives for immunosuppression |
| WO2008079346A1 (en) | 2006-12-21 | 2008-07-03 | Vertex Pharmaceuticals Incorporated | 5-cyan0-4- (pyrrolo [2, 3b] pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors |
| EP2121692B1 (en) | 2006-12-22 | 2013-04-10 | Incyte Corporation | Substituted heterocycles as janus kinase inhibitors |
| US20110160185A9 (en) * | 2007-04-02 | 2011-06-30 | Jorge Salas Solana | Pyrrolopyrimidine derivatives as jak3 inhibitors |
| WO2008157208A2 (en) * | 2007-06-13 | 2008-12-24 | Incyte Corporation | Salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile |
| CL2008001709A1 (es) * | 2007-06-13 | 2008-11-03 | Incyte Corp | Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras. |
| KR20130066703A (ko) * | 2008-02-06 | 2013-06-20 | 노파르티스 아게 | 피롤로［２,３ｄ］피리미딘 및 티로신 키나제 억제제로서 그의 용도 |
| NZ587928A (en) | 2008-03-11 | 2012-08-31 | Incyte Corp | Azetidine and cyclobutane derivatives as jak inhibitors |
| JP5595389B2 (ja) * | 2008-06-20 | 2014-09-24 | ジェネンテック， インコーポレイテッド | トリアゾロピリジンｊａｋ阻害剤化合物と方法 |
| US20100048557A1 (en) * | 2008-06-20 | 2010-02-25 | Bing-Yan Zhu | Triazolopyridine JAK Inhibitor Compounds and Methods |
| CL2009001884A1 (es) * | 2008-10-02 | 2010-05-14 | Incyte Holdings Corp | Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco. |
| JOP20190231A1 (ar) | 2009-01-15 | 2017-06-16 | Incyte Corp | طرق لاصلاح مثبطات انزيم jak و المركبات الوسيطة المتعلقة به |
| CA2752150A1 (en) * | 2009-02-11 | 2010-08-19 | Reaction Biology Corp. | Selective kinase inhibitors |
| AU2010217929B2 (en) * | 2009-02-27 | 2016-07-14 | Ambit Biosciences Corporation | JAK kinase modulating quinazoline derivatives and methods of use thereof |
| EP2432555B1 (en) * | 2009-05-22 | 2014-04-30 | Incyte Corporation | 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 |
| PE20120371A1 (es) | 2009-05-22 | 2012-05-17 | Incyte Corp | 3-[4-(7h-pirrolo[2,3-d]pirimidin-4il)-1h-pirazol-1-il]octano o heptano-nitrilo como inhibidores de jak |
| PL2442809T3 (pl) | 2009-06-17 | 2017-02-28 | Vertex Pharmaceuticals Incorporated | Inhibitory replikacji wirusów grypy |
| CA2767079A1 (en) | 2009-07-08 | 2011-01-13 | Leo Pharma A/S | Heterocyclic compounds as jak receptor and protein tyrosine 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 |
| MX2012004180A (es) * | 2009-10-09 | 2012-07-17 | Incyte Corp | Derivados de hidroxil, ceto y glucuronido de 3-(4-7h-pirrolo[2,3-d ]pirimidin-a-il)-1h-pirazol-1-il)-3-ciclopentilpropanonitrilo. |
| US20110207754A1 (en) * | 2010-02-18 | 2011-08-25 | Incyte Corporation | Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors |
| DK3354652T3 (da) | 2010-03-10 | 2020-05-18 | Incyte Holdings Corp | Piperidin-4-yl azetidinderivativer som jak1-inhibitorer |
| US8518945B2 (en) * | 2010-03-22 | 2013-08-27 | Hoffmann-La Roche Inc. | Pyrrolopyrazine kinase inhibitors |
| PE20130216A1 (es) | 2010-05-21 | 2013-02-27 | Incyte Corp | Formulacion topica para un inhibidor de jak |
| JP5951610B2 (ja) * | 2010-08-27 | 2016-07-13 | 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 | トリアゾロピラジン誘導体 |
| EP2640725B1 (en) | 2010-11-19 | 2015-01-07 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| PH12013501001A1 (en) | 2010-11-19 | 2019-09-02 | Incyte Holdings Corp | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| AU2011343642A1 (en) | 2010-12-16 | 2013-05-02 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| JP2014501772A (ja) * | 2011-01-07 | 2014-01-23 | レオ ファーマ アクティーゼルスカブ | タンパク質チロシンキナーゼ阻害薬としての新規スルファミドピペラジン誘導体およびその医薬用途 |
| CN103732226B (zh) | 2011-02-18 | 2016-01-06 | 诺瓦提斯药物公司 | mTOR/JAK抑制剂组合疗法 |
| JP6277121B2 (ja) | 2011-03-22 | 2018-02-07 | アドヴィナス・セラピューティックス・リミテッド | 置換された縮合三環式化合物、その組成物および医学的応用 |
| AR086983A1 (es) | 2011-06-20 | 2014-02-05 | Incyte Corp | Derivados de azetidinil fenil, piridil o pirazinil carboxamida como inhibidores de jak |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| CA2844507A1 (en) | 2011-08-10 | 2013-02-14 | Novartis Pharma Ag | Jak pi3k/mtor combination therapy |
| 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 |
| US10821111B2 (en) | 2011-11-30 | 2020-11-03 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
| US9089574B2 (en) | 2011-11-30 | 2015-07-28 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
| SI2796460T1 (sl) * | 2011-12-21 | 2018-10-30 | Jiangsu Hengrui Medicine Co. Ltd | Pirolni šestčlenski derivat heteroarilnega obroča, postopek priprave zanj in medicinske uporabe le-tega |
| AR091079A1 (es) | 2012-05-18 | 2014-12-30 | Incyte Corp | Derivados de pirrolopirimidina y pirrolopiridina sustituida con piperidinilciclobutilo como inhibidores de jak |
| US9296757B2 (en) | 2012-05-21 | 2016-03-29 | Bayer Pharma Aktiengesellschaft | Substituted benzothienopyrimidines |
| TW201412740A (zh) | 2012-09-20 | 2014-04-01 | Bayer Pharma AG | 經取代之吡咯并嘧啶胺基苯并噻唑酮 |
| IN2015DN02008A (cg-RX-API-DMAC7.html) | 2012-09-21 | 2015-08-14 | Advinus Therapeutics Ltd | |
| NZ708157A (en) | 2012-11-15 | 2019-07-26 | Incyte Holdings Corp | Sustained-release dosage forms of ruxolitinib |
| SMT201900081T1 (it) | 2013-03-06 | 2019-05-10 | Incyte Holdings Corp | Procedimenti e intermedi per produrre un inibitore di jak |
| WO2014145576A2 (en) | 2013-03-15 | 2014-09-18 | Northwestern University | Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer |
| AU2014277506B2 (en) * | 2013-06-07 | 2017-08-31 | Jiangsu Hengrui Medicine Co., Ltd. | Bisulfate of Janus kinase (JAK) inhibitor and preparation method therefor |
| HRP20200955T1 (hr) | 2013-08-07 | 2020-10-02 | Incyte Corporation | Dozni oblici s produženim oslobađanjem za jak1 inhibitor |
| LT3068776T (lt) | 2013-11-13 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Gripo virusų replikacijos inhibitoriai |
| EP3421468B1 (en) | 2013-11-13 | 2020-11-04 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| 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 |
| CN105524067A (zh) * | 2014-09-28 | 2016-04-27 | 江苏柯菲平医药股份有限公司 | 4-取代吡咯并[2,3-d]嘧啶化合物及其用途 |
| AU2015342444B2 (en) * | 2014-11-05 | 2019-12-12 | Jiangsu Hengrui Medicine Co., Ltd. | Crystalline form of JAK kinase inhibitor bisulfate and a preparation method thereof |
| JP6704416B2 (ja) | 2015-05-13 | 2020-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
| WO2016183120A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| PT3330271T (pt) * | 2015-07-31 | 2022-09-29 | Taiho Pharmaceutical Co Ltd | Composto de pirrolo[2,3-d]pirimidina ou sal do mesmo |
| US10045981B2 (en) | 2015-11-24 | 2018-08-14 | Jakpharm, Llc | Selective kinase inhibitors |
| CN107722012B (zh) | 2016-08-11 | 2020-05-29 | 斯福瑞（南通）制药有限公司 | 制备4-氯-7H-吡咯并[2,3-d]嘧啶的方法 |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| IL276302B2 (en) | 2018-01-30 | 2023-11-01 | Incyte Corp | Procedures for preparing [1-(3-fluoro-2-(trifluoromethyl(isonicotinyl}piperidine-4-one) |
| EP4424328A3 (en) | 2018-03-30 | 2024-12-04 | Incyte Corporation | Treatment of hidradenitis suppurativa using jak inhibitors |
| WO2020257143A1 (en) * | 2019-06-18 | 2020-12-24 | Genentech, Inc. | Pyrazolopyrimidine aryl ether inhibitors of jak kinases and uses thereof |
| AU2020356575A1 (en) | 2019-09-27 | 2022-04-14 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| PE20230251A1 (es) | 2019-11-22 | 2023-02-07 | Incyte Corp | Terapia de combinacion que comprende un inhibidor de alk2 y un inhibidor de jak2 |
| EP4149548A4 (en) | 2020-05-13 | 2024-05-08 | Disc Medicine, Inc. | ANTI-HEMOJUVELIN ANTIBODIES (HJV) FOR THE TREATMENT OF MYELOFIBROSIS |
| EP3915990A1 (en) * | 2020-05-26 | 2021-12-01 | Centre National de la Recherche Scientifique | 4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridine-1-(2h)-carboxamide derivatives as limk and/or rock kinases inhibitors for use in the treatment of cancer |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE247469T1 (de) * | 1995-06-07 | 2003-09-15 | Pfizer | Heterocyclische kondensierte pyrimidin-derivate |
| GB9604361D0 (en) * | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| SK287188B6 (sk) * | 1999-12-10 | 2010-02-08 | Pfizer Products Inc. | Pyrolo [2,3-d]pyrimidínová zlúčenina, jej použitie a farmaceutická kompozícia alebo kombinácia s jej obsahom |
| KR100600550B1 (ko) * | 2000-10-20 | 2006-07-13 | 에자이 가부시키가이샤 | 질소 함유 방향환 유도체 |
| WO2004072063A1 (en) * | 2003-02-07 | 2004-08-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl substituted pyrolls useful as inhibitors of protein kinases |
-
2006
- 2006-02-02 CA CA002596830A patent/CA2596830A1/en not_active Abandoned
- 2006-02-02 US US11/346,048 patent/US8633205B2/en not_active Expired - Fee Related
- 2006-02-02 DE DE602006004844T patent/DE602006004844D1/de active Active
- 2006-02-02 RU RU2007132908/04A patent/RU2434871C2/ru not_active IP Right Cessation
- 2006-02-02 KR KR1020077020046A patent/KR20070104641A/ko not_active Ceased
- 2006-02-02 JP JP2007554283A patent/JP5227032B2/ja not_active Expired - Fee Related
- 2006-02-02 EP EP06734381A patent/EP1844050B1/en not_active Not-in-force
- 2006-02-02 CN CN2006800087780A patent/CN101142218B/zh not_active Expired - Fee Related
- 2006-02-02 ZA ZA200707342A patent/ZA200707342B/xx unknown
- 2006-02-02 AU AU2006221065A patent/AU2006221065A1/en not_active Abandoned
- 2006-02-02 AT AT06734381T patent/ATE420883T1/de active
- 2006-02-02 WO PCT/US2006/004019 patent/WO2006096270A1/en not_active Ceased
- 2006-02-02 ES ES06734381T patent/ES2320487T3/es active Active
- 2006-02-02 MX MX2007009429A patent/MX2007009429A/es active IP Right Grant
-
2007
- 2007-07-29 IL IL184898A patent/IL184898A0/en unknown
- 2007-08-31 NO NO20074431A patent/NO20074431L/no not_active Application Discontinuation
-
2008
- 2008-12-22 JP JP2008326447A patent/JP2009102361A/ja not_active Withdrawn
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2013
- 2013-12-10 US US14/101,543 patent/US20140171454A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190064555A (ko) | 2019-05-31 | 2019-06-10 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
| KR20190096917A (ko) | 2019-08-12 | 2019-08-20 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006096270A1 (en) | 2006-09-14 |
| US20140171454A1 (en) | 2014-06-19 |
| IL184898A0 (en) | 2007-12-03 |
| NO20074431L (no) | 2007-08-31 |
| ES2320487T3 (es) | 2009-05-22 |
| JP2008528705A (ja) | 2008-07-31 |
| DE602006004844D1 (de) | 2009-03-05 |
| JP5227032B2 (ja) | 2013-07-03 |
| ZA200707342B (en) | 2009-03-25 |
| MX2007009429A (es) | 2008-03-18 |
| JP2009102361A (ja) | 2009-05-14 |
| CA2596830A1 (en) | 2006-09-14 |
| EP1844050B1 (en) | 2009-01-14 |
| CN101142218B (zh) | 2013-02-06 |
| AU2006221065A1 (en) | 2006-09-14 |
| EP1844050A1 (en) | 2007-10-17 |
| US8633205B2 (en) | 2014-01-21 |
| US20060183761A1 (en) | 2006-08-17 |
| HK1116349A1 (en) | 2008-12-19 |
| CN101142218A (zh) | 2008-03-12 |
| RU2434871C2 (ru) | 2011-11-27 |
| RU2007132908A (ru) | 2009-03-10 |
| US20070004762A9 (en) | 2007-01-04 |
| ATE420883T1 (de) | 2009-01-15 |
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