RU2448703C2 - Онкогенное ras-специфичное цитотоксическое соединение и способы его применения - Google Patents
Онкогенное ras-специфичное цитотоксическое соединение и способы его применения Download PDFInfo
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- RU2448703C2 RU2448703C2 RU2008125065/15A RU2008125065A RU2448703C2 RU 2448703 C2 RU2448703 C2 RU 2448703C2 RU 2008125065/15 A RU2008125065/15 A RU 2008125065/15A RU 2008125065 A RU2008125065 A RU 2008125065A RU 2448703 C2 RU2448703 C2 RU 2448703C2
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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| RU2008125065A RU2008125065A (ru) | 2009-12-27 |
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Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL212489B1 (pl) * | 2008-01-22 | 2012-10-31 | Univ Jagiellonski | Pochodne fenoksyalkiloaminoalkanoli i ich zastosowania |
| MX2010010871A (es) * | 2008-04-01 | 2010-10-26 | Astellas Pharma Inc | Compuesto de indolinona. |
| BRPI0910198A2 (pt) * | 2008-06-30 | 2016-01-12 | Silenseed Ltd | composição para administração a partir de um sítio local de um agente baseado em nucleotídeos e método para tratar um sujeito sofrendo de uma doença requerendo tratamento local com um agente baseado em nucleotídeo. |
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| US8604074B2 (en) | 2009-01-09 | 2013-12-10 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
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| CA3047125A1 (en) | 2016-12-15 | 2018-06-21 | The Regents Of The University Of California | Compositions and methods for treating cancer |
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| KR102617885B1 (ko) * | 2021-05-07 | 2023-12-27 | 충북대학교 산학협력단 | 신규한 (e)-n'-((1-(4-클로로벤질)-1h-인돌-3-일)메틸렌)-2-(4-옥소퀴나졸린-3(4h)-일)아세토히드라지드 화합물 및 이를 유효성분으로 포함하는 항암제 조성물 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2208607C2 (ru) * | 1999-02-26 | 2003-07-20 | Эйсай Ко., Лтд. | Сульфонамидсодержащие соединения индола |
| US6610722B2 (en) * | 2000-04-10 | 2003-08-26 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US20040138255A1 (en) * | 1999-08-27 | 2004-07-15 | Sugen, Inc. | Phosphate mimics and methods of treatment using phosphatease inhibitors |
| US20050203162A1 (en) * | 2004-03-12 | 2005-09-15 | Miikana Therapeutics Corporation | Cytotoxic agents and methods of use |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4186183A (en) | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
| US4261975A (en) | 1979-09-19 | 1981-04-14 | Merck & Co., Inc. | Viral liposome particle |
| US4485054A (en) | 1982-10-04 | 1984-11-27 | Lipoderm Pharmaceuticals Limited | Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV) |
| US4603044A (en) | 1983-01-06 | 1986-07-29 | Technology Unlimited, Inc. | Hepatocyte Directed Vesicle delivery system |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4957773A (en) | 1989-02-13 | 1990-09-18 | Syracuse University | Deposition of boron-containing films from decaborane |
| US5549910A (en) | 1989-03-31 | 1996-08-27 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5725871A (en) | 1989-08-18 | 1998-03-10 | Danbiosyst Uk Limited | Drug delivery compositions comprising lysophosphoglycerolipid |
| US5707644A (en) | 1989-11-04 | 1998-01-13 | Danbiosyst Uk Limited | Small particle compositions for intranasal drug delivery |
| US5466468A (en) | 1990-04-03 | 1995-11-14 | Ciba-Geigy Corporation | Parenterally administrable liposome formulation comprising synthetic lipids |
| WO1991017424A1 (en) | 1990-05-03 | 1991-11-14 | Vical, Inc. | Intracellular delivery of biologically active substances by means of self-assembling lipid complexes |
| JP3218637B2 (ja) | 1990-07-26 | 2001-10-15 | 大正製薬株式会社 | 安定なリポソーム水懸濁液 |
| JP2958076B2 (ja) | 1990-08-27 | 1999-10-06 | 株式会社ビタミン研究所 | 遺伝子導入用多重膜リポソーム及び遺伝子捕捉多重膜リポソーム製剤並びにその製法 |
| US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5756353A (en) | 1991-12-17 | 1998-05-26 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol-and liposome-based delivery |
| WO1993023011A1 (en) | 1992-05-18 | 1993-11-25 | Minnesota Mining And Manufacturing Company | Transmucosal drug delivery device |
| US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5543158A (en) | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
| ATE170839T1 (de) | 1994-02-22 | 1998-09-15 | Merrell Pharma Inc | Indolderivate zur behandlung von östrogenabhängigen neoplasmen und krankheiten |
| US5534499A (en) | 1994-05-19 | 1996-07-09 | The University Of British Columbia | Lipophilic drug derivatives for use in liposomes |
| US5741516A (en) | 1994-06-20 | 1998-04-21 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US6027726A (en) | 1994-09-30 | 2000-02-22 | Inex Phamaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5580579A (en) | 1995-02-15 | 1996-12-03 | Nano Systems L.L.C. | Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers |
| IE80468B1 (en) | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
| ATE285477T1 (de) | 1995-06-07 | 2005-01-15 | Inex Pharmaceutical Corp | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
| US5738868A (en) | 1995-07-18 | 1998-04-14 | Lipogenics Ltd. | Liposome compositions and kits therefor |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| US20010007877A1 (en) * | 1998-12-16 | 2001-07-12 | George O. Burton | Novel anti-infectives |
| US6900043B1 (en) * | 1999-09-21 | 2005-05-31 | Amgen Inc. | Phosphatases which activate map kinase pathways |
| US6436965B1 (en) * | 2000-03-02 | 2002-08-20 | Merck Frosst Canada & Co. | PDE IV inhibiting amides, compositions and methods of treatment |
| CN1505613A (zh) | 2000-10-10 | 2004-06-16 | ʷ��˿�������ȳ�ķ����˾ | 取代的吲哚、含这类吲哚的药物组合物及它们作为PPAR-γ结合剂的用途 |
| WO2003022274A2 (en) * | 2001-09-13 | 2003-03-20 | Synta Pharmaceuticals Corp. | 2-aroylimidazole compounds for treating cancer |
| WO2004108702A1 (de) * | 2003-06-05 | 2004-12-16 | Zentaris Gmbh | Indolderivate mit apoptose induzierender wirkung |
| EP1484329A1 (de) * | 2003-06-06 | 2004-12-08 | Zentaris GmbH | Indolderivate mit Apoptose induzierender Wirkung |
-
2006
- 2006-11-22 EP EP06840010.0A patent/EP1956910B1/en not_active Not-in-force
- 2006-11-22 RU RU2008125065/15A patent/RU2448703C2/ru not_active IP Right Cessation
- 2006-11-22 US US12/094,739 patent/US8883841B2/en active Active
- 2006-11-22 JP JP2008542528A patent/JP5460054B2/ja not_active Expired - Fee Related
- 2006-11-22 WO PCT/US2006/061219 patent/WO2007062399A2/en not_active Ceased
- 2006-11-22 CA CA2631082A patent/CA2631082C/en not_active Expired - Fee Related
- 2006-11-22 CN CN2006800516184A patent/CN101360422B/zh not_active Expired - Fee Related
- 2006-11-22 AU AU2006318212A patent/AU2006318212C1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2208607C2 (ru) * | 1999-02-26 | 2003-07-20 | Эйсай Ко., Лтд. | Сульфонамидсодержащие соединения индола |
| US20040138255A1 (en) * | 1999-08-27 | 2004-07-15 | Sugen, Inc. | Phosphate mimics and methods of treatment using phosphatease inhibitors |
| US6610722B2 (en) * | 2000-04-10 | 2003-08-26 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US20050203162A1 (en) * | 2004-03-12 | 2005-09-15 | Miikana Therapeutics Corporation | Cytotoxic agents and methods of use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101360422B (zh) | 2013-10-23 |
| JP5460054B2 (ja) | 2014-04-02 |
| JP2009517401A (ja) | 2009-04-30 |
| RU2008125065A (ru) | 2009-12-27 |
| US8883841B2 (en) | 2014-11-11 |
| US20090286847A1 (en) | 2009-11-19 |
| AU2006318212B2 (en) | 2012-01-12 |
| EP1956910A2 (en) | 2008-08-20 |
| CA2631082C (en) | 2015-02-03 |
| WO2007062399A2 (en) | 2007-05-31 |
| CN101360422A (zh) | 2009-02-04 |
| AU2006318212C1 (en) | 2012-08-30 |
| AU2006318212A1 (en) | 2007-05-31 |
| EP1956910B1 (en) | 2014-09-17 |
| WO2007062399A3 (en) | 2007-12-21 |
| CA2631082A1 (en) | 2007-05-31 |
| EP1956910A4 (en) | 2010-03-24 |
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