KR20020084254A - 상승효과가 있는 암치료 방법 및 조성물 - Google Patents
상승효과가 있는 암치료 방법 및 조성물 Download PDFInfo
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- KR20020084254A KR20020084254A KR1020027012704A KR20027012704A KR20020084254A KR 20020084254 A KR20020084254 A KR 20020084254A KR 1020027012704 A KR1020027012704 A KR 1020027012704A KR 20027012704 A KR20027012704 A KR 20027012704A KR 20020084254 A KR20020084254 A KR 20020084254A
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- South Korea
- Prior art keywords
- compound
- tetrahydro
- benzodiazepine
- ylmethyl
- imidazol
- 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.)
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
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- 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
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
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- 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
- C07D403/02—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 two hetero rings
- C07D403/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| PCT/US2001/009193 WO2001072721A2 (en) | 2000-03-27 | 2001-03-22 | Synergistic methods and compositions for treating cancer |
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| KR20020084254A true KR20020084254A (ko) | 2002-11-04 |
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Families Citing this family (108)
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| WO1998022461A1 (de) * | 1996-11-18 | 1998-05-28 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Epothilone c, d, e und f, deren herstellung und deren verwendung als cytostatische mittel bzw. als pflanzenschutzmittel |
| JP4579351B2 (ja) * | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| US6204388B1 (en) | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6867305B2 (en) * | 1996-12-03 | 2005-03-15 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US20050043376A1 (en) * | 1996-12-03 | 2005-02-24 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| AU2002211427A1 (en) * | 2000-10-05 | 2002-04-15 | Whitehead Institute For Biomedical Research | Effects of combined administration of farnesyl transferase inhibitors and signal transduction inhibitors |
| AU2002214649A1 (en) * | 2000-10-16 | 2002-04-29 | Neopharm, Inc. | Liposomal formulation of mitoxantrone |
| US7037906B1 (en) * | 2000-12-22 | 2006-05-02 | Oxigene, Inc. | Methods for modulating tumor growth and metastasis |
| US20050209310A1 (en) * | 2000-12-22 | 2005-09-22 | Chaplin David J | Methods for modulating tumor growth and metastasis |
| CZ305799B6 (cs) * | 2001-03-14 | 2016-03-23 | Bristol-Myers Squibb Company | Kombinace analogů epothilonu a chemoterapeutických činidel pro léčení proliferačních nemocí |
| CA2444867C (en) * | 2001-05-16 | 2010-08-17 | Novartis Ag | Combination comprising n-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2pyrimidine-amine and a chemotherapeutic agent |
| DE60224299T2 (de) * | 2001-10-25 | 2008-12-11 | Novartis Ag | Kombinationsmedikationen mit einem selektiven cyclooxygenase-2-inhibitor |
| GB0126879D0 (en) * | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| US7074921B2 (en) * | 2001-11-13 | 2006-07-11 | Bristol Myers Squibb Company | Process for the preparation of 3,7-disubstituted-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine compounds |
| TW200408407A (en) * | 2001-11-30 | 2004-06-01 | Dana Farber Cancer Inst Inc | Methods and compositions for modulating the immune system and uses thereof |
| KR20040066921A (ko) * | 2001-12-20 | 2004-07-27 | 브리스톨-마이어스스퀴브컴파니 | 생체이용률이 향상된 경구 활성 탁산 유도체의 제약조성물 |
| US20030147813A1 (en) * | 2002-02-07 | 2003-08-07 | John Lyons | Method for treating chronic myelogenous leukemia |
| US6998391B2 (en) * | 2002-02-07 | 2006-02-14 | Supergen.Inc. | Method for treating diseases associated with abnormal kinase activity |
| MXPA04010640A (es) * | 2002-05-17 | 2005-08-16 | Aventis Pharma Sa | Uso de docetaxel/doxorrubicina/ciclofosfamida en la terapia adyuvante de cancer de mama y ovario. |
| EP2316922B1 (en) * | 2002-05-24 | 2013-05-22 | Merck Sharp & Dohme Corp. | Neutralizing human anti-IGFR antibody |
| US6627614B1 (en) * | 2002-06-05 | 2003-09-30 | Super Gen, Inc. | Sequential therapy comprising a 20(S)-camptothecin and an anthracycline |
| RU2379032C9 (ru) * | 2002-06-10 | 2010-03-27 | Новартис Аг | Комбинации, включающие эпотилоны, и их фармацевтическое применение |
| PL372070A1 (en) * | 2002-06-10 | 2005-07-11 | Novartis Ag | Combinations comprising epothilones and pharmaceutical uses thereof |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CA2496477C (en) * | 2002-08-23 | 2012-10-16 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US7649006B2 (en) * | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US20040209930A1 (en) * | 2002-10-02 | 2004-10-21 | Carboni Joan M. | Synergistic methods and compositions for treating cancer |
| GB0223380D0 (en) * | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| US8613922B2 (en) | 2003-04-24 | 2013-12-24 | The University Of North Carolina At Chapel Hill | Methods for inhibiting diabetic retinopathy with an antibody against integrin associated protein (IAP) |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| WO2005000230A2 (en) * | 2003-06-05 | 2005-01-06 | Charles Achkar | Methods of treating hyperproliferative cell disorders |
| EP1493445A1 (en) * | 2003-07-04 | 2005-01-05 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of stress-induced ligand-dependent EGFR activation |
| NZ601544A (en) * | 2003-08-27 | 2013-11-29 | Ophthotech Corp | Combination therapy for the treatment of ocular neovascular disorders |
| US7326567B2 (en) | 2003-11-12 | 2008-02-05 | Schering Corporation | Plasmid system for multigene expression |
| WO2005046665A1 (en) * | 2003-11-13 | 2005-05-26 | Warner-Lambert Company Llc | Combination chemotherapy comprising a mek inhibitor and a erbb1/2 receptor inhibitor |
| AR046639A1 (es) * | 2003-11-21 | 2005-12-14 | Schering Corp | Combinaciones terapeuticas de anticuerpo anti- igfr1 |
| US7612071B2 (en) * | 2004-03-12 | 2009-11-03 | Syntrix Biosystems, Inc. | Compositions and methods employing aminopterin |
| EP1732549A4 (en) * | 2004-03-18 | 2009-11-11 | Brigham & Womens Hospital | METHOD FOR THE TREATMENT OF SYNUCLEINOPATHIES |
| WO2005089518A2 (en) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Uch-l1 expression and cancer therapy |
| JP2007538004A (ja) * | 2004-03-18 | 2007-12-27 | ザ ブライハム アンド ウイメンズ ホスピタル， インコーポレイテッド | シヌクレイノパチーを治療する方法 |
| WO2005089515A2 (en) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| US20070293539A1 (en) * | 2004-03-18 | 2007-12-20 | Lansbury Peter T | Methods for the treatment of synucleinopathies |
| WO2005089502A2 (en) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| KR20060130764A (ko) * | 2004-03-23 | 2006-12-19 | 아스트라제네카 아베 | 병용 요법 |
| GB0406446D0 (en) * | 2004-03-23 | 2004-04-28 | Astrazeneca Ab | Combination therapy |
| ATE478894T1 (de) * | 2004-04-15 | 2010-09-15 | Genencor Int | Anti-cea scfv-beta-lactamase konstrukte (cab moleküle) in adept |
| US7449196B2 (en) * | 2004-07-09 | 2008-11-11 | Robert Sabin | Anti tumor compositions and methods of use |
| JP2008506681A (ja) * | 2004-07-16 | 2008-03-06 | ファイザー・プロダクツ・インク | 抗ｉｇｆ−１ｒ抗体を用いる非血液性の悪性腫瘍の併用療法 |
| GB0419071D0 (en) | 2004-08-26 | 2004-09-29 | Mgx Internat Ltd | Display device |
| GB0424339D0 (en) * | 2004-11-03 | 2004-12-08 | Astrazeneca Ab | Combination therapy |
| TW200628156A (en) * | 2004-11-04 | 2006-08-16 | Bristol Myers Squibb Co | Combination of a SRC kinase inhibitor and a BCR-ABL inhibitor for the treatment of proliferative diseases |
| EP2283831A3 (en) * | 2004-12-03 | 2013-10-23 | Merck Sharp & Dohme Corp. | Biomakers for pre-selection of patients for anti-IGF1R therapy |
| PT1839662E (pt) * | 2005-01-19 | 2010-04-28 | Zeria Pharm Co Ltd | Agente antitumoral |
| ZA200706804B (en) * | 2005-02-03 | 2008-10-29 | Gen Hospital Corp | Method for treating gefitinib resistant cancer |
| JP2008536479A (ja) | 2005-02-11 | 2008-09-11 | ユニバーシティ オブ サザン カリフォルニア | ジスルフィド架橋を有するタンパク質の発現法 |
| US20060194821A1 (en) * | 2005-02-18 | 2006-08-31 | The Brigham And Women's Hospital, Inc. | Compounds inhibiting the aggregation of superoxide dismutase-1 |
| RU2276613C1 (ru) * | 2005-03-17 | 2006-05-20 | Российская медицинская академия последипломного образования Министерства здравоохранения Российской Федерации (РМАПО МЗ РФ) | Способ лечения злокачественных опухолей головки поджелудочной железы |
| US20060235006A1 (en) * | 2005-04-13 | 2006-10-19 | Lee Francis Y | Combinations, methods and compositions for treating cancer |
| EP1879587A2 (en) * | 2005-04-15 | 2008-01-23 | Schering Corporation | Methods and compositions for treating or preventing cancer |
| DK1877102T3 (da) * | 2005-04-28 | 2014-07-21 | Danisco Us Inc | Tab-molekyler |
| AR053272A1 (es) | 2005-05-11 | 2007-04-25 | Hoffmann La Roche | Determinacion de responsivos a la quimioterapia |
| CN101287761A (zh) * | 2005-06-15 | 2008-10-15 | 先灵公司 | 抗-igf1r抗体制剂 |
| FR2887454B1 (fr) * | 2005-06-28 | 2009-06-05 | Sanofi Aventis Sa | Combinaisons antitumorales contenant des derives du taxane et des sigma ligands |
| CA2626326C (en) | 2005-11-04 | 2021-02-16 | Wyeth | Antineoplastic combinations with mtor inhibitor, herceptin, and/or hki-272 |
| US8546404B2 (en) | 2005-12-13 | 2013-10-01 | Merck Sharp & Dohme | Compounds that are ERK inhibitors |
| MX2008010635A (es) | 2006-02-16 | 2008-10-28 | Schering Corp | Derivados de pirrolidina como inhibidores de cinasa regulada por señales extracelulares. |
| WO2007103828A2 (en) * | 2006-03-02 | 2007-09-13 | The Board Of Regents Of The University Of Texas System | Fluorocytidine derivatives and cox-2 inhibitors for the treatment of cancer |
| US8008256B2 (en) * | 2006-05-01 | 2011-08-30 | University Of Southern California | Combination therapy for treatment of cancer |
| RU2325914C2 (ru) * | 2006-06-15 | 2008-06-10 | Государственное учреждение научно-исследовательский институт онкологии Томского Научного центра Сибирского отделения Российской академии медицинских наук (ГУ НИИ онкологии ТНЦ СО РАМН) | Способ лечения операбельного рака молочной железы |
| US20080081051A1 (en) * | 2006-09-28 | 2008-04-03 | Robert Sabin | Method of manufacturing anti-tumor and anti-viral compositions |
| US20080085881A1 (en) * | 2006-10-06 | 2008-04-10 | Aimery De Gramont | Stop-and-go oxaliplatin treatment regimens |
| WO2008065409A2 (en) * | 2006-12-01 | 2008-06-05 | Betagenon Ab | Combination for use in the treatment of cancer, comprising tamoxifen or an aromatase inhibitor |
| EP2131849B1 (en) * | 2007-03-02 | 2011-10-26 | The University Of Wollongong | Compositions and methods for delivery of anti-cancer agents |
| WO2008115478A2 (en) * | 2007-03-19 | 2008-09-25 | University Of Medicine And Dentistry Of New Jersey | Method of cancer detection and treatment |
| WO2009035718A1 (en) * | 2007-09-10 | 2009-03-19 | Curis, Inc. | Tartrate salts or complexes of quinazoline based egfr inhibitors containing a zinc binding moiety |
| WO2009033204A1 (en) * | 2007-09-12 | 2009-03-19 | University Of Wollongong | Multi-component compositions and methods for delivery of anti-cancer agents |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| ES2402138T3 (es) | 2007-12-28 | 2013-04-29 | Deutsches Krebsforschungszentrum, Stiftung Des Öffentlichen Rechts | Terapia contra el cáncer con un parvovirus combinado con quimioterapia |
| USRE45471E1 (en) * | 2008-01-28 | 2015-04-14 | Nanocarrier Co., Ltd. | Pharmaceutical composition or combination drug |
| WO2009105500A1 (en) | 2008-02-21 | 2009-08-27 | Schering Corporation | Compounds that are erk inhibitors |
| WO2009151683A2 (en) * | 2008-03-12 | 2009-12-17 | Link Medicine Corporation | Quinolinone farnesyl transferase inhibitors for the treatment of synucleinopathies and other indications |
| CA2725390C (en) * | 2008-04-08 | 2014-09-23 | Syndax Pharmaceuticals, Inc. | Use of a hdac inhibitor and a her-2 inhibitor in the treatment of breast cancer |
| RU2365370C1 (ru) * | 2008-04-29 | 2009-08-27 | Государственное учреждение Российский онкологический научный центр им. Н.Н. Блохина РАМН | Способ лечения рака легкого |
| DK2310011T3 (da) * | 2008-06-17 | 2013-10-14 | Wyeth Llc | Antineoplastiske kombinationer indeholdende hki-272 og vinorelbin |
| WO2010057006A1 (en) * | 2008-11-13 | 2010-05-20 | Link Medicine Corporation | Azaquinolinone derivatives and uses thereof |
| US20110060005A1 (en) * | 2008-11-13 | 2011-03-10 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| US8802394B2 (en) | 2008-11-13 | 2014-08-12 | Radu O. Minea | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
| US20100331363A1 (en) * | 2008-11-13 | 2010-12-30 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| EP2370103B1 (en) * | 2008-11-28 | 2016-03-23 | Novartis AG | Pharmaceutical combinations comprising an isoxazole derived hsp90-inhibitor and the her2 inhibitor trastuzumab |
| EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| WO2010099364A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| US20110300150A1 (en) | 2010-05-18 | 2011-12-08 | Scott Eliasof | Compositions and methods for treatment of autoimmune and other disease |
| EP2500036B1 (en) * | 2011-03-18 | 2014-05-07 | Metheresis Translational Research SA | MET inhibitors for enhancing radiotherapy efficacy |
| JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 癌薬剤発見、診断、および治療におけるｅｍｔ遺伝子シグネチャーの使用 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| CN103374000B (zh) * | 2012-04-13 | 2015-11-11 | 中国科学院广州生物医药与健康研究院 | 嘧啶并二氮杂卓类化合物及其药用组合物和应用 |
| SG10201912985RA (en) | 2013-07-12 | 2020-02-27 | Ophthotech Corp | Methods for treating or preventing ophthalmological conditions |
| CN107043456B (zh) * | 2017-04-19 | 2019-05-17 | 川北医学院 | 对氧环己酮与l-苯丙氨酸氮芥共聚物及其应用 |
| CA3068256A1 (en) | 2017-06-21 | 2018-12-27 | The University Of North Carolina At Chapel Hill | Methods and compositions for chimeric antigen receptor targeting cancer cells |
| CA3103130A1 (en) | 2018-06-13 | 2019-12-19 | The University Of North Carolina At Chapel Hill | Methods and compositions for chimeric antigen receptor targeting cancer cells |
| US11068254B1 (en) | 2020-06-10 | 2021-07-20 | Cigna Intellectual Property, Inc. | Systems and methods for generating and managing domain-based technology architecture |
| WO2022256656A1 (en) * | 2021-06-03 | 2022-12-08 | University Of Cincinnati | Bzd-1 as a chemosensitizer of cancer |
| CN120695174A (zh) * | 2021-07-01 | 2025-09-26 | 江苏先声生物制药有限公司 | 抗人vegf抗体与化药联用在制备治疗卵巢癌的药物中的应用 |
| US11879010B2 (en) | 2021-09-30 | 2024-01-23 | The Charlotte Mecklenburg Hospital Authority | Methods and compositions for pretargeted immunotherapy |
| CN114712377B (zh) * | 2022-04-26 | 2023-08-15 | 江苏师范大学 | 断血流皂苷a在制造药物中的用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6011029A (en) * | 1996-02-26 | 2000-01-04 | Bristol-Myers Squibb Company | Inhibitors of farnesyl protein transferase |
| DE19706584C2 (de) * | 1997-02-21 | 2002-09-26 | Aeg Energietechnik Gmbh | Hochtemperaturbrennstoffzellen mit Erwärmung des Reaktionsgases |
| GB9801231D0 (en) | 1997-06-05 | 1998-03-18 | Merck & Co Inc | A method of treating cancer |
| WO1999002573A1 (en) * | 1997-07-08 | 1999-01-21 | Union Carbide Chemicals & Plastics Technology Cor Poration | Method for reducing sheeting during olefin polymerization |
| CZ298511B6 (cs) | 1997-12-22 | 2007-10-24 | Schering Corporation | Použití benzocykloheptapyridinových sloucenin proprípravu farmaceutického prípravku pro použití v kombinaci s antineoplastickým lécivem a/nebo radioterapií k lécení proliferacních onemocnení |
| TR200102109T2 (tr) * | 1999-01-21 | 2001-12-21 | Bristol-Myers Squibb Company | Ras-farnesiltransferazı inhibitörü ve sülfobütileter-7-ß-siklodekstrin veya 2-hidroksipropil-ß-siklodekstrin kompleksi ve metod. |
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| AU2001247683B2 (en) | 2006-01-12 |
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