RU2452469C2 - Составы бензимидазолилпиридилэфиров - Google Patents
Составы бензимидазолилпиридилэфиров Download PDFInfo
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- RU2452469C2 RU2452469C2 RU2009105819/15A RU2009105819A RU2452469C2 RU 2452469 C2 RU2452469 C2 RU 2452469C2 RU 2009105819/15 A RU2009105819/15 A RU 2009105819/15A RU 2009105819 A RU2009105819 A RU 2009105819A RU 2452469 C2 RU2452469 C2 RU 2452469C2
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- -1 Benzimidazolylpyridyl ester compounds Chemical class 0.000 title claims description 69
- 239000000203 mixture Substances 0.000 claims abstract description 370
- 150000001875 compounds Chemical class 0.000 claims abstract description 177
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- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 25
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 22
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 36
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 22
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Landscapes
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| TW200804345A (en) * | 2005-08-30 | 2008-01-16 | Novartis Ag | Substituted benzimidazoles and methods of preparation |
| PE20130814A1 (es) * | 2006-08-30 | 2013-08-08 | Novartis Ag | Sales de benzimidazolil piridil eteres y formulaciones que las contienen |
| MX2009009344A (es) * | 2007-03-02 | 2009-09-11 | Novartis Ag | Formas solidas de un inhibidor de cinasa raf. |
| WO2010040055A2 (en) * | 2008-10-03 | 2010-04-08 | Intekrin Therapeutics, Inc. | Oral pharmaceutical formulations for antidiabetic compounds |
| JO3434B1 (ar) * | 2009-07-31 | 2019-10-20 | Millennium Pharm Inc | مركبات صيدلانية لمعالجة السرطان وامراض واضطرابات اخري |
| JP5936609B2 (ja) * | 2010-06-29 | 2016-06-22 | ベラステム インコーポレイテッド | キナーゼインヒビターの経口製剤 |
| WO2012012139A1 (en) | 2010-06-30 | 2012-01-26 | Poniard Pharmaceuticals, Inc. | Synthesis and use of kinase inhibitors |
| CN102336740B (zh) * | 2010-07-27 | 2013-07-24 | 中国科学院上海药物研究所 | 一类咪唑类化合物及其用途 |
| CN103301067B (zh) * | 2012-03-15 | 2018-09-11 | 苏州泽璟生物制药有限公司 | 一种改善吸收性能的固体分散体及其制备 |
| EP2976086B1 (en) | 2013-03-22 | 2020-10-14 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mtorc 1/2 inhibitors and selective inhibitors of aurora a kinase |
| US10561627B2 (en) * | 2014-12-31 | 2020-02-18 | Eric Morrison | Ibuprofen nanoparticle carriers encapsulated with hermetic surfactant films |
| KR20220070057A (ko) | 2015-03-09 | 2022-05-27 | 인테크린 테라퓨틱스, 아이엔씨. | 비알코올성 지방간 질환 및/또는 지방이영양증의 치료 방법 |
| SG11201909046XA (en) | 2017-04-03 | 2019-10-30 | Coherus Biosciences Inc | PPARγ AGONIST FOR TREATMENT OF PROGRESSIVE SUPRANUCLEAR PALSY |
| US12053447B2 (en) | 2019-06-25 | 2024-08-06 | NuBioPharma, LLC | Oral solution and powder to liquid compositions of balsalazide |
Citations (1)
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| EA014230B1 (ru) * | 2005-08-30 | 2010-10-29 | Новартис Аг | Замещенные бензимидазолы в качестве ингибиторов киназ |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9401090D0 (en) | 1994-01-21 | 1994-03-16 | Glaxo Lab Sa | Chemical compounds |
| KR0179401B1 (ko) * | 1994-02-28 | 1999-03-20 | 송택선 | 신규한 5-피롤릴-2-피리딜메틸설피닐벤즈이미다졸 유도체 |
| US6391636B1 (en) | 1994-05-31 | 2002-05-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US6358932B1 (en) | 1994-05-31 | 2002-03-19 | Isis Pharmaceticals, Inc. | Antisense oligonucleotide inhibition of raf gene expression |
| US6037136A (en) | 1994-10-24 | 2000-03-14 | Cold Spring Harbor Laboratory | Interactions between RaF proto-oncogenes and CDC25 phosphatases, and uses related thereto |
| US5717100A (en) | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
| IL127210A0 (en) | 1996-05-23 | 1999-09-22 | Applied Research Systems | Compounds inhibiting the binding of raf-1 or 13-3-3 proteins to the beta-chain of il-2 pharmaceutical compositions containing them and their use |
| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US6187799B1 (en) | 1997-05-23 | 2001-02-13 | Onyx Pharmaceuticals | Inhibition of raf kinase activity using aryl ureas |
| GB9716557D0 (en) | 1997-08-06 | 1997-10-08 | Glaxo Group Ltd | Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity |
| US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
| US6204467B1 (en) | 1998-03-24 | 2001-03-20 | Ford Global Technologies, Inc. | Method and apparatus for resistive welding |
| ME00275B (me) | 1999-01-13 | 2011-02-10 | Bayer Corp | ω-KARBOKSIARIL SUPSTITUISANI DIFENIL KARBAMIDI KAO INHIBITORI RAF KINAZE |
| US6391683B1 (en) * | 2000-06-21 | 2002-05-21 | Siliconware Precision Industries Co., Ltd. | Flip-chip semiconductor package structure and process for fabricating the same |
| US6756410B2 (en) | 2000-08-30 | 2004-06-29 | Kamal D. Mehta | Induction of LDL receptor expression by extracellular-signal regulated kinase, ERK-1/2 |
| TWI293877B (en) * | 2000-09-20 | 2008-03-01 | Rtp Pharma Inc | Spray drying process and compositions of fenofibrate |
| US20040131670A1 (en) * | 2001-04-17 | 2004-07-08 | Ping Gao | Pellicle-resistant gelatin capsule |
| US20030198666A1 (en) * | 2002-01-07 | 2003-10-23 | Richat Abbas | Oral insulin therapy |
| GB0205693D0 (en) * | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| US8299108B2 (en) | 2002-03-29 | 2012-10-30 | Novartis Ag | Substituted benzazoles and methods of their use as inhibitors of raf kinase |
| DK1499311T3 (da) | 2002-03-29 | 2010-03-08 | Novartis Vaccines & Diagnostic | Substituerede benzaboler og anvendelse deraf som RAF-kinaseinhibitorer |
| US20050082192A1 (en) * | 2002-06-17 | 2005-04-21 | Eric Smarr | End cap support for jumbo rolls of material |
| US7846959B2 (en) * | 2004-05-07 | 2010-12-07 | Exelixis, Inc. | Raf modulators and methods of use |
| US20100231394A1 (en) * | 2009-03-11 | 2010-09-16 | Bobby Eugene Finchum | Carbon monoxide detection and dissipation apparatus |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EA014230B1 (ru) * | 2005-08-30 | 2010-10-29 | Новартис Аг | Замещенные бензимидазолы в качестве ингибиторов киназ |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101516335B (zh) | 2014-01-08 |
| EP2046292A2 (en) | 2009-04-15 |
| AU2007275634A1 (en) | 2008-01-24 |
| ATE459338T1 (de) | 2010-03-15 |
| HRP20100293T1 (hr) | 2010-06-30 |
| PT2046292E (pt) | 2010-04-26 |
| WO2008011154A3 (en) | 2008-06-26 |
| RU2012107218A (ru) | 2013-09-10 |
| WO2008011154A2 (en) | 2008-01-24 |
| AU2007275634B2 (en) | 2011-01-20 |
| SI2046292T1 (sl) | 2010-06-30 |
| RU2009105819A (ru) | 2010-08-27 |
| EP2046292B1 (en) | 2010-03-03 |
| ES2340631T3 (es) | 2010-06-07 |
| CN101516335A (zh) | 2009-08-26 |
| JP2009544617A (ja) | 2009-12-17 |
| CA2657346A1 (en) | 2008-01-24 |
| MX2009000770A (es) | 2009-01-28 |
| DE602007005139D1 (de) | 2010-04-15 |
| CY1110037T1 (el) | 2015-01-14 |
| KR20090033904A (ko) | 2009-04-06 |
| DK2046292T3 (da) | 2010-06-07 |
| US20100040677A1 (en) | 2010-02-18 |
| PL2046292T3 (pl) | 2010-08-31 |
| US8455662B2 (en) | 2013-06-04 |
| BRPI0715423A2 (pt) | 2013-07-02 |
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