ES2475741T3 - Ciclopropil dicarboxamidas y análogos que presentan actividades antic�ncer y antiproliferativas - Google Patents
Ciclopropil dicarboxamidas y análogos que presentan actividades antic�ncer y antiproliferativas Download PDFInfo
- Publication number
- ES2475741T3 ES2475741T3 ES11719421.7T ES11719421T ES2475741T3 ES 2475741 T3 ES2475741 T3 ES 2475741T3 ES 11719421 T ES11719421 T ES 11719421T ES 2475741 T3 ES2475741 T3 ES 2475741T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- cyclopropane
- dicarboxamide
- compound
- fluorophenyl
- 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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- 230000001028 anti-proliverative effect Effects 0.000 title description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title description 3
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- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims abstract description 8
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- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 6
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims abstract description 6
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- WOVFQJQCMLCIDS-UHFFFAOYSA-N 1-n'-[4-(2-acetamidopyridin-4-yl)oxy-2,5-difluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)F)=C1 WOVFQJQCMLCIDS-UHFFFAOYSA-N 0.000 claims description 6
- GNNDEPIMDAZHRQ-UHFFFAOYSA-N 1-n'-[4-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-2,5-difluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C(=CC(OC=3C=C(NC(=O)C4CC4)N=CC=3)=C(F)C=2)F)CC1 GNNDEPIMDAZHRQ-UHFFFAOYSA-N 0.000 claims description 6
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- CIVOREZLHOQUQB-CQSZACIVSA-N 1-n'-[2,5-difluoro-4-[2-[[(2r)-2-methoxypropanoyl]amino]pyridin-4-yl]oxyphenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)[C@@H](C)OC)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)F)=C1 CIVOREZLHOQUQB-CQSZACIVSA-N 0.000 claims description 4
- ASBXOTJHWOHLPN-UHFFFAOYSA-N 1-n'-[4-[2-(2,2-dimethylpropanoylamino)pyridin-4-yl]oxy-2,5-difluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)C(C)(C)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)F)=C1 ASBXOTJHWOHLPN-UHFFFAOYSA-N 0.000 claims description 4
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- XGGWHIQZALFGOB-UHFFFAOYSA-N 1-n'-[2,5-difluoro-4-[2-(2-methylpropanoylamino)pyridin-4-yl]oxyphenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)C(C)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)F)=C1 XGGWHIQZALFGOB-UHFFFAOYSA-N 0.000 claims description 3
- PORMSSHVBFZGAT-UHFFFAOYSA-N 1-n'-[4-(2-acetamidopyridin-4-yl)oxy-2,5-difluorophenyl]-1-n-phenylcyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC=CC=3)=C(F)C=2)F)=C1 PORMSSHVBFZGAT-UHFFFAOYSA-N 0.000 claims description 3
- PRXXUUDSMHUXSS-UHFFFAOYSA-N 1-n'-[4-[2-(cyclobutanecarbonylamino)pyridin-4-yl]oxy-2,5-difluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C(=CC(OC=3C=C(NC(=O)C4CCC4)N=CC=3)=C(F)C=2)F)CC1 PRXXUUDSMHUXSS-UHFFFAOYSA-N 0.000 claims description 3
- 206010027406 Mesothelioma Diseases 0.000 claims description 3
- WLBRCFBAWZUERA-CYBMUJFWSA-N 1-n'-[2,5-difluoro-4-[2-[[(2r)-2-hydroxypropanoyl]amino]pyridin-4-yl]oxyphenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)[C@H](O)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)F)=C1 WLBRCFBAWZUERA-CYBMUJFWSA-N 0.000 claims description 2
- VJSYQFGUDJRCMR-UHFFFAOYSA-N 1-n'-[4-(2-acetamidopyridin-4-yl)oxy-5-chloro-2-fluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=NC(NC(=O)C)=CC(OC=2C(=CC(NC(=O)C3(CC3)C(=O)NC=3C=CC(F)=CC=3)=C(F)C=2)Cl)=C1 VJSYQFGUDJRCMR-UHFFFAOYSA-N 0.000 claims description 2
- FWYCTAYGNLLRHZ-UHFFFAOYSA-N 2-fluoro-2-methylpropanamide Chemical compound CC(C)(F)C(N)=O FWYCTAYGNLLRHZ-UHFFFAOYSA-N 0.000 claims description 2
- MTEZLAATISORQK-UHFFFAOYSA-N 2-methoxyacetamide Chemical compound COCC(N)=O MTEZLAATISORQK-UHFFFAOYSA-N 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
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- 208000033781 Thyroid carcinoma Diseases 0.000 claims 1
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- 201000004101 esophageal cancer Diseases 0.000 claims 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 118
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 52
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/14—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 containing three or more hetero rings
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- Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| US32954810P | 2010-04-29 | 2010-04-29 | |
| US329548P | 2010-04-29 | ||
| PCT/US2011/034556 WO2011137342A1 (en) | 2010-04-29 | 2011-04-29 | Cyclopropyl dicarboxamides and analogs exhibiting anti-cancer and anti-proliferative activites |
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| ES2475741T3 true ES2475741T3 (es) | 2014-07-11 |
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| CN102256493A (zh) * | 2008-10-29 | 2011-11-23 | 迪赛孚尔制药有限公司 | 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物 |
| DK2563362T3 (da) * | 2010-04-29 | 2014-06-23 | Deciphera Pharmaceuticals Llc | Cyclopropyldicarboxamider og analoger heraf, der udviser anticancer og antiproliferativ aktivitet |
| CN102702120A (zh) * | 2012-04-06 | 2012-10-03 | 浙江工业大学 | 一种新化合物邻羟基苯基四嗪二甲酰胺及制备和应用 |
| CN102702121B (zh) * | 2012-04-06 | 2016-04-13 | 浙江工业大学 | 一种化合物间羟基苯基四嗪二甲酰胺及制备和应用 |
| US20150119402A1 (en) | 2012-05-08 | 2015-04-30 | The Regents Of The University Of California | Alpha 7 nicotinic acetylcholine allosteric modulators, their derivatives and uses thereof |
| US8461179B1 (en) | 2012-06-07 | 2013-06-11 | Deciphera Pharmaceuticals, Llc | Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| EP3327144B1 (en) | 2013-02-25 | 2020-03-25 | Novartis AG | Novel androgen receptor mutation |
| WO2014145023A1 (en) * | 2013-03-15 | 2014-09-18 | Deciphera Pharmaceuticals, Llc | 1,2,4-triazol-5-ones and analogs exhibiting anti-cancer and anti-proliferative activities |
| WO2016061231A1 (en) * | 2014-10-14 | 2016-04-21 | Deciphera Pharmaceuticals, Llc | Inhibition of tumor cell interactions with the microenvironment resulting in a reduction in tumor growth and disease progression |
| US20160101090A1 (en) * | 2014-10-14 | 2016-04-14 | Deciphera Pharmaceuticals, Llc | Inhibition of trk kinase mediated tumor growth and disease progression |
| US20170079966A1 (en) * | 2014-10-14 | 2017-03-23 | Deciphera Pharmaceuticals, Llc | Inhibition of tumor cell interactions with the microenvironment resulting in a reduction in tumor growth and disease progression |
| JP2019513700A (ja) | 2016-03-16 | 2019-05-30 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 殺有害生物剤及び植物保護剤としてのｎ−（シアノベンジル）−６−（シクロプロピル−カルボニルアミノ）−４−（フェニル）−ピリジン−２−カルボキサミド誘導体及び関連する化合物 |
| CN106349158B (zh) * | 2016-08-03 | 2020-02-28 | 杭州市西溪医院 | 一种c-Met小分子抑制剂、含其的药物组合物及其药学应用 |
| CN107793363B (zh) * | 2016-09-06 | 2021-02-26 | 上海医药工业研究院 | 一种取代芳胺基芳杂环类化合物及其作为抗肿瘤药物的应用 |
| CN106831707B (zh) * | 2016-12-28 | 2019-09-20 | 杭州市西溪医院 | 作为c-Met激酶抑制剂的苯并杂环类衍生物及其医疗用途 |
| US10180422B1 (en) | 2017-08-22 | 2019-01-15 | Scripps Health | Methods of treating a neuroendocrine tumor |
| CN109988108B (zh) * | 2017-12-29 | 2022-04-29 | 江苏豪森药业集团有限公司 | 一种卡博替尼的制备方法 |
| AU2019216351B2 (en) | 2018-01-31 | 2024-07-25 | Deciphera Pharmaceuticals, Llc | Combination therapy for the treatment of mastocytosis |
| EP3746059B1 (en) | 2018-01-31 | 2026-03-04 | Deciphera Pharmaceuticals, LLC | Combination therapy for the treatment of gastrointestinal stromal tumors |
| KR20210119411A (ko) | 2018-12-28 | 2021-10-05 | 데시페라 파마슈티칼스, 엘엘씨. | 암 치료에 사용하기 위한 csf1r 억제제 |
| WO2020185812A1 (en) | 2019-03-11 | 2020-09-17 | Teva Pharmaceuticals International Gmbh | Solid state forms of ripretinib |
| EP3966207B1 (en) | 2019-05-10 | 2023-11-01 | Deciphera Pharmaceuticals, LLC | Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof |
| EP3966206B1 (en) | 2019-05-10 | 2023-08-09 | Deciphera Pharmaceuticals, LLC | Heteroarylaminopyrimidine amide autophagy inhibitors and methods of use thereof |
| JP7626722B2 (ja) | 2019-06-17 | 2025-02-04 | デシフェラ・ファーマシューティカルズ，エルエルシー | アミノピリミジンアミドオートファジー阻害剤およびその使用方法 |
| TWI878335B (zh) | 2019-08-12 | 2025-04-01 | 美商迪賽孚爾製藥有限公司 | 治療胃腸道基質瘤方法 |
| FI4013412T3 (fi) | 2019-08-12 | 2026-03-24 | Deciphera Pharmaceuticals Llc | Ripretinibi ruoansulatuskanavan stroomakasvaimien hoitoon |
| PL4084779T3 (pl) | 2019-12-30 | 2025-02-24 | Deciphera Pharmaceuticals, Llc | Kompozycje 1-(4-bromo-5-(1-etylo-7-(metyloamino)-2-okso-1,2-dihydro-1,6-naftyrydyn-3-ylo)-2-fluorofenylo)-3-fenylomocznika |
| AU2020419197B2 (en) | 2019-12-30 | 2023-08-31 | Deciphera Pharmaceuticals, Llc | Amorphous kinase inhibitor formulations and methods of use thereof |
| JP2023549540A (ja) | 2020-11-18 | 2023-11-27 | デシフェラ・ファーマシューティカルズ，エルエルシー | Ｇｃｎ２およびｐｅｒｋキナーゼ阻害剤およびその使用方法 |
| PE20250609A1 (es) | 2021-12-03 | 2025-02-26 | Deciphera Pharmaceuticals Llc | Inhibidores de gcn2 y perk quinasa y metodos de uso de los mismos |
| US12319655B2 (en) | 2021-12-09 | 2025-06-03 | Deciphera Pharmaceuticals, Llc | RAF kinase inhibitors and methods of use thereof |
| CN114394940B (zh) * | 2022-01-26 | 2024-01-16 | 武汉工程大学 | 一种环丙基-1,1二酰胺类化合物及其制备方法和应用 |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
| WO2025122942A1 (en) | 2023-12-08 | 2025-06-12 | Deciphera Pharmaceuticals, Llc | Solid state forms of a kinase inhibitor |
| US20250205161A1 (en) | 2023-12-08 | 2025-06-26 | Deciphera Pharmaceuticals, Llc | Formulations of vimseltinib |
| WO2025231106A1 (en) | 2024-05-01 | 2025-11-06 | Deciphera Pharmaceuticals, Llc | Csf-1r inhibitors and methods of use thereof |
| WO2025231105A1 (en) | 2024-05-01 | 2025-11-06 | Deciphera Pharmaceuticals, Llc | Processes of making csf-1r inhibitors and methods of use thereof |
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| EP1719762B1 (en) | 2004-02-27 | 2012-06-27 | Eisai R&D Management Co., Ltd. | Novel pyridine derivative and pyrimidine derivative (1) |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| PL1889836T3 (pl) * | 2005-08-24 | 2013-10-31 | Eisai R&D Man Co Ltd | Nowa pochodna pirydyny i pochodna pirymidyny (3) |
| AR059246A1 (es) | 2006-01-30 | 2008-03-19 | Array Biopharma Inc | Compuestos heterobiciclicos de tiofeno y metodos de uso |
| CN101454311B (zh) | 2006-08-23 | 2013-03-27 | 卫材R&D管理有限公司 | 苯氧基吡啶衍生物的盐和其结晶及其制备方法 |
| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| US7790756B2 (en) | 2006-10-11 | 2010-09-07 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| WO2008046216A1 (en) | 2006-10-18 | 2008-04-24 | Methylgene, Inc. | Kinase inhibitors and uses thereof |
| CA2679602A1 (en) | 2007-02-23 | 2008-08-28 | Eisai R&D Management Co., Ltd. | Pyridine or pyrimidine derivative having excellent cell growth inhibition effect and excellent anti-tumor effect on cell strain having amplification of hgfr gene |
| CN101918403A (zh) | 2007-09-06 | 2010-12-15 | 阵列生物制药公司 | 作为酪氨酸激酶抑制剂的吡唑并吡啶类化合物 |
| JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| US20090227556A1 (en) * | 2008-01-31 | 2009-09-10 | Eisai R&D Management Co., Ltd. | Receptor tyrosine kinase inhibitors comprising pyridine and pyrimidine derivatives |
| JPWO2009104520A1 (ja) | 2008-02-18 | 2011-06-23 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | フェノキシピリジン誘導体の製造方法（２） |
| AR075084A1 (es) * | 2008-09-26 | 2011-03-09 | Smithkline Beecham Corp | Metodo de preparacion de quinolinil -oxidifenil - ciclopropanodicarboxamidas e intermediarios correspondientes |
| CN102256493A (zh) * | 2008-10-29 | 2011-11-23 | 迪赛孚尔制药有限公司 | 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物 |
| WO2010064300A1 (ja) | 2008-12-02 | 2010-06-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 食道癌治療用組成物 |
| JP2010178651A (ja) | 2009-02-04 | 2010-08-19 | Eisai R & D Management Co Ltd | Ｈｇｆｒ阻害物質の作用検定方法 |
| DK2563362T3 (da) * | 2010-04-29 | 2014-06-23 | Deciphera Pharmaceuticals Llc | Cyclopropyldicarboxamider og analoger heraf, der udviser anticancer og antiproliferativ aktivitet |
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2011
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- 2011-04-29 WO PCT/US2011/034556 patent/WO2011137342A1/en not_active Ceased
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- 2011-04-29 SG SG2012079760A patent/SG185073A1/en unknown
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- 2011-04-29 JP JP2013508280A patent/JP5795630B2/ja not_active Expired - Fee Related
- 2011-04-29 CN CN201180031486.XA patent/CN103068384B/zh not_active Expired - Fee Related
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- 2011-04-29 EP EP11719421.7A patent/EP2563362B1/en not_active Not-in-force
- 2011-04-29 PT PT117194217T patent/PT2563362E/pt unknown
- 2011-04-29 SG SG10201503394PA patent/SG10201503394PA/en unknown
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2015
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Also Published As
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| MX2012012571A (es) | 2013-04-05 |
| CN103068384A (zh) | 2013-04-24 |
| US20120252849A1 (en) | 2012-10-04 |
| JP5795630B2 (ja) | 2015-10-14 |
| US20120058985A1 (en) | 2012-03-08 |
| US20120322834A1 (en) | 2012-12-20 |
| HK1184392A1 (zh) | 2014-01-24 |
| EP2563362B1 (en) | 2014-03-12 |
| US20140194405A1 (en) | 2014-07-10 |
| WO2011137342A1 (en) | 2011-11-03 |
| RU2012151012A (ru) | 2014-06-10 |
| DK2563362T3 (da) | 2014-06-23 |
| US8637672B2 (en) | 2014-01-28 |
| SG185073A1 (en) | 2012-12-28 |
| CN103068384B (zh) | 2015-03-11 |
| PH12012502142A1 (en) | 2017-04-21 |
| AU2011245248B2 (en) | 2016-01-07 |
| KR20130109943A (ko) | 2013-10-08 |
| IL222728A0 (en) | 2012-12-31 |
| BR112012027743A2 (pt) | 2017-03-14 |
| JP2013525458A (ja) | 2013-06-20 |
| AU2011245248A1 (en) | 2012-12-20 |
| SG10201503394PA (en) | 2015-06-29 |
| PT2563362E (pt) | 2014-07-11 |
| EP2563362A1 (en) | 2013-03-06 |
| CA2800569A1 (en) | 2011-11-03 |
| US20150218130A1 (en) | 2015-08-06 |
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