JP2011518836A - 大環状化合物およびそれらのキナーゼ阻害剤としての使用 - Google Patents
大環状化合物およびそれらのキナーゼ阻害剤としての使用 Download PDFInfo
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- JP2011518836A JP2011518836A JP2011506453A JP2011506453A JP2011518836A JP 2011518836 A JP2011518836 A JP 2011518836A JP 2011506453 A JP2011506453 A JP 2011506453A JP 2011506453 A JP2011506453 A JP 2011506453A JP 2011518836 A JP2011518836 A JP 2011518836A
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- Prior art keywords
- chloro
- docosa
- nonaen
- tetraazatetracyclo
- pentaazatetracyclo
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| PCT/US2009/041555 WO2009132202A2 (en) | 2008-04-24 | 2009-04-23 | Macrocyclic compounds and their use as kinase inhibitors |
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| JP2016041709A (ja) * | 2012-03-06 | 2016-03-31 | ファイザー・インク | 増殖性疾患の治療のための大環状誘導体 |
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| WO2016073847A2 (en) * | 2014-11-07 | 2016-05-12 | The Regents Of The University Of Michigan | Inhibitors of myocardin-related transcription factor and serum response factor (mrtf/srf)-mediated gene transcription and methods for use of the same |
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| ES2819869T3 (es) | 2015-10-08 | 2021-04-19 | Bayer Pharma AG | Nuevos compuestos macrocíclicos modificados |
| WO2017060322A2 (en) | 2015-10-10 | 2017-04-13 | Bayer Pharma Aktiengesellschaft | Ptefb-inhibitor-adc |
| GB2560713A (en) * | 2017-03-20 | 2018-09-26 | Eternygen Gmbh | Inhibitor of citrate transporter |
| ES2900199T3 (es) | 2017-03-28 | 2022-03-16 | Bayer Ag | Novedosos compuestos macrocíclicos inhibidores de PTEFB |
| EP3601236A1 (en) | 2017-03-28 | 2020-02-05 | Bayer Aktiengesellschaft | Novel ptefb inhibiting macrocyclic compounds |
| TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
| US10793554B2 (en) | 2018-10-29 | 2020-10-06 | Forma Therapeutics, Inc. | Solid forms of 4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone |
| CN113784713A (zh) * | 2019-01-11 | 2021-12-10 | 纳吉斯制药股份有限公司 | 白三烯合成抑制剂 |
| EA202192575A1 (ru) | 2019-03-21 | 2022-01-14 | Онксео | Соединения dbait в сочетании с ингибиторами киназ для лечения рака |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| CN114761006A (zh) | 2019-11-08 | 2022-07-15 | Inserm(法国国家健康医学研究院) | 对激酶抑制剂产生耐药性的癌症的治疗方法 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| US20230148005A1 (en) * | 2020-02-18 | 2023-05-11 | Theseus Pharmaceuticals, Inc. | Macrocyclic compounds and uses thereof |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| CN113698408B (zh) * | 2020-05-22 | 2025-07-25 | 武汉朗来科技发展有限公司 | Jnk抑制剂、其药物组合物和用途 |
| CN113735856A (zh) * | 2020-05-29 | 2021-12-03 | 百极弘烨(南通)医药科技有限公司 | 大环jak抑制剂及其应用 |
| CN113549113A (zh) * | 2020-06-17 | 2021-10-26 | 广州百霆医药科技有限公司 | 一种含膦大环化合物及其制备方法与应用 |
| CN114805371B (zh) * | 2021-01-19 | 2024-05-24 | 江苏开元药业有限公司 | 含2-氨基嘧啶大环类化合物及其制备方法和用途 |
| CN118139846A (zh) * | 2021-09-23 | 2024-06-04 | 河南晟翔医药科技有限公司 | 一种egfr小分子抑制剂、含其的药物组合物及其用途 |
| WO2023113510A1 (ko) * | 2021-12-15 | 2023-06-22 | 환인제약 주식회사 | 마크로사이클릭 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 신경 퇴행성 질환의 예방 또는 치료용 약학적 조성물 |
| CN114394974B (zh) * | 2022-03-25 | 2022-12-06 | 中国药科大学 | 多取代三芳基大环化合物与应用 |
| EP4568951A1 (en) * | 2022-08-08 | 2025-06-18 | Ajax Therapeutics, Inc. | Heterocyclic amide and urea compounds as jak2 inhibitors |
| WO2024094171A1 (zh) * | 2022-11-04 | 2024-05-10 | 江苏恒瑞医药股份有限公司 | 取代的氨基嘧啶类化合物、其制备方法及其在医药上的应用 |
| CN116496234B (zh) * | 2023-02-09 | 2024-09-13 | 江苏润安制药有限公司 | 一种盐酸乌拉地尔关键中间体的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006501271A (ja) * | 2002-08-21 | 2006-01-12 | シエーリング アクチエンゲゼルシャフト | 大環状ピリミジン類、それらの生成及び医薬剤 |
| WO2006061415A1 (en) * | 2004-12-08 | 2006-06-15 | Janssen Pharmaceutica N.V. | 2,4 (4,6) pyrimidine derivatives |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| AU4231299A (en) | 1998-06-04 | 1999-12-20 | Abbott Laboratories | Cell adhesion-inhibiting antinflammatory compounds |
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| PT1107964E (pt) | 1998-08-11 | 2010-06-11 | Novartis Ag | Derivados de isoquinolina com actividade inibidora da angiogénese |
| US6133031A (en) | 1999-08-19 | 2000-10-17 | Isis Pharmaceuticals Inc. | Antisense inhibition of focal adhesion kinase expression |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| DE60037345T2 (de) | 1999-12-10 | 2008-11-13 | Pfizer Products Inc., Groton | Pyrrolo(2,3-d)pyrimidin-Verbindungen |
| WO2001047922A2 (en) | 1999-12-24 | 2001-07-05 | Aventis Pharma Limited | Azaindoles |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0011527D0 (en) | 2000-05-12 | 2000-06-28 | Unilever Plc | Bleach catalyst and composition and method for bleaching a substrate |
| KR100786927B1 (ko) | 2000-06-28 | 2007-12-17 | 스미스클라인비이참피이엘시이 | 습식 분쇄방법 |
| BR0212760A (pt) | 2001-09-19 | 2004-12-07 | Aventis Pharma Sa | Compostos quìmicos |
| DE60213842T2 (de) | 2001-10-30 | 2007-09-06 | Novartis Ag | Staurosporin-derivate als hemmer der flt3-rezeptor-tyrosinkinase-wirkung |
| PE20040522A1 (es) | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| WO2004011422A1 (en) | 2002-07-25 | 2004-02-05 | University Of Florida | Method for incorporation of pentafluorosulfanyl (sf5) substituents into aliphatic and aromatic compounds |
| TWI335913B (en) | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
| UA80767C2 (en) | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| JP2006518381A (ja) | 2003-02-07 | 2006-08-10 | 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 | プロテインキナーゼのインヒビターとして有用なヘテロアリール置換ピロール |
| WO2004078682A2 (en) | 2003-03-05 | 2004-09-16 | Irm Llc | Cyclic compounds and compositions as protein kinase inhibitors |
| ES2263862T3 (es) | 2003-03-07 | 2006-12-16 | Istituto Nazionale Per Lo Studio E La Cura Dei Tumori | Ensayo de quinasa de linfoma anaplasico, sus reactivos y composiciones. |
| GB0305929D0 (en) | 2003-03-14 | 2003-04-23 | Novartis Ag | Organic compounds |
| SE0301373D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Novel compounds |
| SE0301372D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Novel compounds |
| GB0316109D0 (en) | 2003-07-09 | 2003-08-13 | Dystar Textilfarben Gmbh & Co | Water-soluble macrocyclic azacalixarenes |
| GB0316915D0 (en) | 2003-07-18 | 2003-08-20 | Glaxo Group Ltd | Compounds |
| EP1660087A2 (en) | 2003-07-22 | 2006-05-31 | Janssen Pharmaceutica N.V. | Quinolinone derivatives as inhibitors of c-fms kinase |
| DE10333183A1 (de) | 2003-07-22 | 2005-02-17 | Daimlerchrysler Ag | Verfahren zum Betrieb eines Antriebsstranges für ein Kraftfahrzeug |
| AR045944A1 (es) | 2003-09-24 | 2005-11-16 | Novartis Ag | Derivados de isoquinolina 1.4-disustituidas |
| JP2005220116A (ja) | 2004-02-09 | 2005-08-18 | Japan Science & Technology Agency | １，３，５−トリアジン環を環構成要素として含むシクロファン型化合物、その製造方法、中間体及びその利用 |
| WO2005113556A1 (en) | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| AU2005309019A1 (en) | 2004-11-24 | 2006-06-01 | Novartis Ag | Combinations of JAK inhibitors and at least one of Bcr-Abl, Flt-3, FAK or RAF kinase inhibitors |
| EP1674470A1 (en) | 2004-12-22 | 2006-06-28 | Schering Aktiengesellschaft | Sulfonamido-macrocycles as Tie2 inhibitors |
| US20060194823A1 (en) | 2004-12-22 | 2006-08-31 | Georg Kettschau | Sulfonamido-macrocycles as Tie2 inhibitors and the salts thereof, a pharmaceutical composition comprising these compounds, the method of preparing and the use thereof |
| EP1710246A1 (en) | 2005-04-08 | 2006-10-11 | Schering Aktiengesellschaft | Sulfoximine-pyrimidine Macrocycles and the salts thereof, a process for making them, and their pharmaceutical use against cancer |
| US8778919B2 (en) | 2005-06-30 | 2014-07-15 | Janssen Pharmaceutica Nv | Cyclic anilino—pyridinotriazines |
| WO2007058627A1 (en) | 2005-11-16 | 2007-05-24 | S*Bio Pte Ltd | Oxygen linked pyrimidine derivatives |
| SG10202003901UA (en) | 2005-12-13 | 2020-05-28 | Incyte Holdings Corp | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors |
| EP1803723A1 (de) | 2006-01-03 | 2007-07-04 | Bayer Schering Pharma Aktiengesellschaft | (2,4,9-triaza-1(2,4)-pyrimidina-3(1,3)-benzenacyclononaphan-3^4-yl)-sulfoximid derivate als selektive inhibitoren der aurora kinase zur behandlung von krebs |
| EP1870416A1 (en) | 2006-06-21 | 2007-12-26 | Bayer Schering Pharma Aktiengesellschaft | Sulphonamido-macrocycles as tie2 inhibitors |
| EP1873159A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Substituted sulphonamido-macrocycles as Tie2 inhibitors and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
-
2009
- 2009-04-23 EP EP09734200A patent/EP2274288A2/en not_active Withdrawn
- 2009-04-23 JP JP2011506453A patent/JP2011518836A/ja active Pending
- 2009-04-23 WO PCT/US2009/041555 patent/WO2009132202A2/en not_active Ceased
- 2009-04-23 US US12/429,014 patent/US8871753B2/en not_active Expired - Fee Related
- 2009-04-23 CA CA2722326A patent/CA2722326A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006501271A (ja) * | 2002-08-21 | 2006-01-12 | シエーリング アクチエンゲゼルシャフト | 大環状ピリミジン類、それらの生成及び医薬剤 |
| WO2006061415A1 (en) * | 2004-12-08 | 2006-06-15 | Janssen Pharmaceutica N.V. | 2,4 (4,6) pyrimidine derivatives |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016041709A (ja) * | 2012-03-06 | 2016-03-31 | ファイザー・インク | 増殖性疾患の治療のための大環状誘導体 |
| JP2016505069A (ja) * | 2013-01-25 | 2016-02-18 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｃ型肝炎の治療用のアンモニウム誘導体 |
| JP2016540824A (ja) * | 2013-12-20 | 2016-12-28 | インスティテュート オブ ファーマコロジー アンド トキシコロジー アカデミー オブ ミリタリー メディカル サイエンシズ ピー．エル．エー．チャイナ | 新規ピペリジンカルボキサミド化合物、その調製方法及び使用 |
| JP2023513793A (ja) * | 2020-02-14 | 2023-04-03 | ソーク インスティテュート フォー バイオロジカル スタディーズ | 大環状ｕｌｋ１／２阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| US8871753B2 (en) | 2014-10-28 |
| US20090286778A1 (en) | 2009-11-19 |
| EP2274288A2 (en) | 2011-01-19 |
| CA2722326A1 (en) | 2009-10-29 |
| WO2009132202A3 (en) | 2010-11-25 |
| WO2009132202A2 (en) | 2009-10-29 |
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