JP4755759B2 - ４−ｈ−１−ベンゾピラン−４−オン誘導体の平滑筋細胞増殖インヒビターとしての使用 - Google Patents
４−ｈ−１−ベンゾピラン−４−オン誘導体の平滑筋細胞増殖インヒビターとしての使用 Download PDFInfo
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- JP4755759B2 JP4755759B2 JP2000595666A JP2000595666A JP4755759B2 JP 4755759 B2 JP4755759 B2 JP 4755759B2 JP 2000595666 A JP2000595666 A JP 2000595666A JP 2000595666 A JP2000595666 A JP 2000595666A JP 4755759 B2 JP4755759 B2 JP 4755759B2
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- alkyl
- alkylamino
- flavopiridol
- phenyl
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24338099A | 1999-02-01 | 1999-02-01 | |
| US09/243,380 | 1999-02-01 | ||
| US09/468,665 US6399633B1 (en) | 1999-02-01 | 1999-12-21 | Use of 4-H-1-benzopryan-4-one derivatives as inhibitors of smooth muscle cell proliferation |
| US09/468,665 | 1999-12-21 | ||
| PCT/US2000/001104 WO2000044362A2 (en) | 1999-02-01 | 2000-01-18 | The use of 4-h-1-benzopyran-4-one derivatives as inhibitors of smooth muscle cell proliferation |
Publications (3)
| Publication Number | Publication Date |
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| JP2002535356A JP2002535356A (ja) | 2002-10-22 |
| JP2002535356A5 JP2002535356A5 (enExample) | 2007-03-01 |
| JP4755759B2 true JP4755759B2 (ja) | 2011-08-24 |
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Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0102480D0 (en) * | 2001-01-31 | 2001-03-14 | Cyclacel Ltd | Marker |
| WO2003088903A2 (en) * | 2002-04-17 | 2003-10-30 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| US7425618B2 (en) | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| US20040106647A1 (en) * | 2002-06-28 | 2004-06-03 | Schneider Michael D. | Modulators of Cdk9 as a therapeutic target in cardiac hypertrophy |
| AU2003280090A1 (en) * | 2002-06-28 | 2004-01-19 | Baylor College Of Medicine | Modulators of cdk9 as a therapeutic target in cardiac hypertrophy |
| JP4596916B2 (ja) * | 2002-09-05 | 2010-12-15 | メディミューン，エルエルシー | Ｃｄ２拮抗薬を投与することによりｔ細胞悪性腫瘍を予防または治療する方法 |
| US8034831B2 (en) | 2002-11-06 | 2011-10-11 | Celgene Corporation | Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies |
| US7563810B2 (en) | 2002-11-06 | 2009-07-21 | Celgene Corporation | Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases |
| JP4764818B2 (ja) | 2003-04-11 | 2011-09-07 | メディミューン，エルエルシー | 組換えｉｌ−９抗体およびその使用 |
| WO2005042743A2 (en) | 2003-08-18 | 2005-05-12 | Medimmune, Inc. | Humanization of antibodies |
| US20060228350A1 (en) * | 2003-08-18 | 2006-10-12 | Medimmune, Inc. | Framework-shuffling of antibodies |
| AU2005299355A1 (en) | 2004-10-27 | 2006-05-04 | Medimmune, Llc | Modulation of antibody specificity by tailoring the affinity to cognate antigens |
| JP5153613B2 (ja) | 2005-03-18 | 2013-02-27 | メディミューン，エルエルシー | 抗体のフレームワーク・シャッフル |
| JP2008546805A (ja) | 2005-06-23 | 2008-12-25 | メディミューン，エルエルシー | 最適な凝集および断片化プロフィールを有する抗体製剤 |
| US20100068238A1 (en) * | 2005-07-15 | 2010-03-18 | Nandkishore Managoli | Implantable Medical Devices Comprising a Flavonoid or Derivative Thereof for Prevention of Restenosis |
| JP2008255008A (ja) * | 2005-07-19 | 2008-10-23 | Tokyo Medical & Dental Univ | 滑膜細胞増殖抑制剤 |
| CA2617213C (en) * | 2005-07-29 | 2014-01-28 | Resverlogix Corp. | Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices |
| NZ596091A (en) | 2006-08-28 | 2012-07-27 | Jolla Inst Allergy Immunolog | Antagonistic human light-specific human monoclonal antibodies |
| KR101444489B1 (ko) | 2007-02-01 | 2014-09-24 | 리스버로직스 코퍼레이션 | 심혈관 질환을 예방 및 치료하기 위한 화합물 |
| US20110130544A1 (en) | 2007-03-30 | 2011-06-02 | Medimmune, Llc | Antibodies with decreased deamidation profiles |
| WO2009158404A1 (en) | 2008-06-26 | 2009-12-30 | Resverlogix Corp. | Methods of preparing quinazolinone derivatives |
| WO2010079431A2 (en) | 2009-01-08 | 2010-07-15 | Resverlogix Corp. | Compounds for the prevention and treatment of cardiovascular disease |
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| CN107252429B (zh) | 2009-04-22 | 2023-06-16 | 雷斯韦洛吉克斯公司 | 新抗炎剂 |
| EP2593099A1 (en) | 2010-07-12 | 2013-05-22 | DKFZ Deutsches Krebsforschungszentrum | Wogonin for the prevention and therapy of cardiac hypertrophy |
| DK2668210T3 (da) | 2011-01-26 | 2020-08-24 | Celldex Therapeutics Inc | Anti-kit antistoffer og anvendelser deraf |
| DK2773354T3 (da) | 2011-11-01 | 2019-08-05 | Resverlogix Corp | Oralformuleringer med øjeblikkelig frigivelse for substituerede quinazolinoner |
| RU2681730C2 (ru) | 2012-07-25 | 2019-03-12 | Селлдекс Терапьютикс Инк. | Антитела против kit и их применения |
| SG11201502757QA (en) | 2012-10-09 | 2015-05-28 | Igenica Biotherapeutics Inc | Anti-c16orf54 antibodies and methods of use thereof |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| AU2013365926B9 (en) | 2012-12-21 | 2019-01-17 | Zenith Epigenetics Ltd. | Novel heterocyclic compounds as bromodomain inhibitors |
| EP3003390B1 (en) | 2013-06-06 | 2021-07-07 | Pierre Fabre Médicament | Anti-c10orf54 antibodies and uses thereof |
| LT3041507T (lt) | 2013-08-26 | 2021-08-25 | Biontech Research And Development, Inc. | Nukleorūgštys, koduojančios antikūnus prieš sialil-lewis a |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| CA3121083C (en) | 2014-06-04 | 2023-08-15 | Biontech Research And Development, Inc. | Human monoclonal antibodies to ganglioside gd2 |
| SI3333191T1 (sl) | 2014-12-11 | 2021-03-31 | Pierre Fabre Medicament | Proti C10ORF54 protitelesa in uporaba le-teh |
| FI3265123T3 (fi) | 2015-03-03 | 2023-01-31 | Vasta-aineita, käyttöjä & menetelmiä | |
| KR102662814B1 (ko) | 2015-03-13 | 2024-05-03 | 리스버로직스 코퍼레이션 | 보체 관련 질환을 치료하기 위한 조성물 및 치료 방법 |
| MX2017013383A (es) | 2015-04-20 | 2017-12-07 | Tolero Pharmaceuticals Inc | Prediccion de respuesta a alvocidib mediante perfilado mitocondrial. |
| PL3298021T3 (pl) | 2015-05-18 | 2019-11-29 | Tolero Pharmaceuticals Inc | Proleki alvocidibu o zwiększonej biodostępności |
| MX2018001289A (es) | 2015-08-03 | 2018-04-30 | Tolero Pharmaceuticals Inc | Terapias de combinacion para el tratamiento del cancer. |
| WO2017096017A1 (en) | 2015-12-02 | 2017-06-08 | Stsciences, Inc. | Antibodies specific to glycosylated btla (b- and t- lymphocyte attenuator) |
| WO2017096051A1 (en) | 2015-12-02 | 2017-06-08 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
| KR102466192B1 (ko) | 2016-08-23 | 2022-11-14 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 간세포성 암종의 치료를 위한 조합 요법 |
| US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
| WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| RU2764724C2 (ru) | 2017-03-16 | 2022-01-19 | ЭИСАЙ Р энд Д МЕНЕДЖМЕНТ КО., ЛТД. | Комбинированная терапия для лечения рака молочной железы |
| EP3630835A1 (en) | 2017-05-31 | 2020-04-08 | STCube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
| US12215151B2 (en) | 2017-05-31 | 2025-02-04 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that immunospecifically bind to BTN1A1 |
| JP2020522562A (ja) | 2017-06-06 | 2020-07-30 | ストキューブ アンド シーオー．， インコーポレイテッド | Ｂｔｎ１ａ１又はｂｔｎ１ａ１リガンドに結合する抗体及び分子を用いて癌を治療する方法 |
| WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
| JP7256796B2 (ja) | 2017-10-13 | 2023-04-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｔｈｏｍｓｅｎ－ｎｏｕｖｅｌｌｅ（ｔｎ）抗原に対するヒト抗体 |
| CN112740043A (zh) | 2018-07-20 | 2021-04-30 | 皮埃尔法布雷医药公司 | Vista受体 |
| AU2019391097B2 (en) | 2018-12-04 | 2025-07-03 | Sumitomo Pharma America, Inc. | CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
| WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
| CN113559244B (zh) * | 2021-08-02 | 2023-12-26 | 华中科技大学同济医学院附属协和医院 | Ctrp13脂肪因子的新用途 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62242680A (ja) * | 1986-04-11 | 1987-10-23 | ヘキスト・アクチエンゲゼルシヤフト | ４ｈ−１−ベンゾピラン−４−オン誘導体およびその製法 |
| US5284856A (en) * | 1988-10-28 | 1994-02-08 | Hoechst Aktiengesellschaft | Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives |
| WO1997016447A1 (en) * | 1995-10-31 | 1997-05-09 | Mitotix, Inc. | Inhibitors of cyclin-dependent kinases |
| WO1998013344A1 (en) * | 1996-09-26 | 1998-04-02 | Bristol-Myers Squibb Company | A process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5849733A (en) | 1996-05-10 | 1998-12-15 | Bristol-Myers Squibb Co. | 2-thio or 2-oxo flavopiridol analogs |
| DE69839338T2 (de) | 1997-02-05 | 2008-07-10 | Warner-Lambert Company Llc | Pyrido (2,3-d) pyrimidine und 4-amino-pyrimidine als inhibitoren der zellulären proliferation |
-
1999
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62242680A (ja) * | 1986-04-11 | 1987-10-23 | ヘキスト・アクチエンゲゼルシヤフト | ４ｈ−１−ベンゾピラン−４−オン誘導体およびその製法 |
| US5284856A (en) * | 1988-10-28 | 1994-02-08 | Hoechst Aktiengesellschaft | Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives |
| WO1997016447A1 (en) * | 1995-10-31 | 1997-05-09 | Mitotix, Inc. | Inhibitors of cyclin-dependent kinases |
| WO1998013344A1 (en) * | 1996-09-26 | 1998-04-02 | Bristol-Myers Squibb Company | A process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs |
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