ES2608829T3 - Inhibidores de tirosina quinasa que contienen diarilacetileno hidrazida - Google Patents
Inhibidores de tirosina quinasa que contienen diarilacetileno hidrazida Download PDFInfo
- Publication number
- ES2608829T3 ES2608829T3 ES12701370.4T ES12701370T ES2608829T3 ES 2608829 T3 ES2608829 T3 ES 2608829T3 ES 12701370 T ES12701370 T ES 12701370T ES 2608829 T3 ES2608829 T3 ES 2608829T3
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- Prior art keywords
- alkyl
- ring
- aryl
- methyl
- ethynyl
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- 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 4
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- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 63
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- 125000003118 aryl group Chemical group 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 38
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 34
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 30
- 125000005843 halogen group Chemical group 0.000 claims abstract description 21
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 14
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- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 14
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 13
- 125000006413 ring segment Chemical group 0.000 claims abstract description 13
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- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 21
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 20
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 claims description 19
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 10
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- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
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- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 3
- SNBGAYPZHYYXRH-UHFFFAOYSA-N 2,6-dichloro-n'-[3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzoyl]benzohydrazide Chemical compound C1=C(C#CC=2N3N=CC=CC3=NC=2)C(C)=CC=C1C(=O)NNC(=O)C1=C(Cl)C=CC=C1Cl SNBGAYPZHYYXRH-UHFFFAOYSA-N 0.000 claims description 2
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- MBVAHHOKMIRXLP-UHFFFAOYSA-N imidazo[1,2-a]pyrazine Chemical compound C1=CN=CC2=NC=CN21 MBVAHHOKMIRXLP-UHFFFAOYSA-N 0.000 claims description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
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- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
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- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/18—Halogen atoms or nitro radicals
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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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
- C07D401/02—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 two hetero rings
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- Public Health (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyridine Compounds (AREA)
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| PCT/GB2012/050132 WO2012098416A1 (en) | 2011-01-21 | 2012-01-23 | Diarylacetylene hydrazide containing tyrosine kinase inhibitors |
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| EP4238566A1 (en) | 2012-05-02 | 2023-09-06 | Georgetown University | Treating amyotrophic lateral sclerosis with tyrosine kinase inhibitors |
| CN103664787B (zh) * | 2012-09-17 | 2015-09-09 | 南京圣和药业股份有限公司 | 炔杂芳环化合物及其应用 |
| EP2818471A1 (en) * | 2013-06-27 | 2014-12-31 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Nitrogen bicyclic compounds as inhibitors for Scyl1 and Grk5 |
| GB2518873A (en) * | 2013-10-03 | 2015-04-08 | Agency Science Tech & Res | Bicyclic alkyne derivatives and uses thereof |
| JP6744218B2 (ja) | 2013-11-15 | 2020-08-19 | ザ ウィスター インスティテュート オブ アナトミー アンド バイオロジー | Ebna1阻害剤およびそれらの使用方法 |
| KR102616818B1 (ko) | 2015-05-14 | 2023-12-22 | 더 위스타 인스티튜트 오브 아나토미 앤드 바이올로지 | Ebna1 억제제 및 그의 사용 방법 |
| US10150733B2 (en) * | 2015-05-18 | 2018-12-11 | Sun Pharma Advanced Research Company Ltd. | Amidoheteroaryl aroyl hydrazide ethynes |
| CA3014740C (en) * | 2016-02-16 | 2021-06-01 | Korea Institute Of Science And Technology | 2,3,5-substituted thiophene compound as protein kinase inhibitor |
| JP6974357B2 (ja) * | 2016-06-02 | 2021-12-01 | スン プハルマ アドバンセド リサーチ カンパニー リミテド | パーキンソン病の治療 |
| EA037697B1 (ru) * | 2016-06-02 | 2021-05-12 | Сан Фарма Адвансед Ресёрч Компани Лимитед | Лечение болезни паркинсона |
| EP3596050A4 (en) * | 2017-03-15 | 2021-01-13 | Sun Pharma Advanced Research Company Limited | NEW SOAP DISPERSION OF HYDRAZIDE N'- (2-CHLORO-6-METHYL-BENZOYL) 4-METHYL-3-QUINOLINE-3-YLETHYNYL-BENZOIC ACID |
| US11273126B2 (en) | 2017-03-15 | 2022-03-15 | Sun Pharma Advanced Research Company Limited | Amorphous dispersion of cyclopropanecarboxylic acid (5-{5-[N′-(2-chloro-6-methylbenzoyl) hydrazinocarbonyl]-2-methyl-phenylethynyl}-pyridin-2-yl) amide |
| WO2019222470A1 (en) | 2018-05-17 | 2019-11-21 | The Wistar Institute | Ebna1 inhibitor crystalline forms, and methods of preparing and using same |
| WO2020106825A1 (en) | 2018-11-20 | 2020-05-28 | Georgetown University | Compositions and methods for treating neurodegenerative, myodegenerative, and lysosomal storage disorders |
| PH12021553098A1 (en) | 2019-06-11 | 2023-08-14 | Sun Pharma Advanced Res Co Ltd | Treatment for synucleinopathies |
| WO2021129565A1 (en) * | 2019-12-26 | 2021-07-01 | Beijing Innocare Pharma Tech Co., Ltd. | Crystalline forms of (s) -1- (1-acryloylpyrrolidin-3-yl) -3- ( (3, 5-dimethoxyphenyl) ethynyl) -5- (methylamino) -1h-pyrazole-4-carboxamide |
| JP7505719B2 (ja) | 2020-02-28 | 2024-06-25 | テグ-キョンプク メディカル イノベーション ファウンデーション | 3-((8-((1H-ピラゾール-4-イル)アミノ)イミダゾ[1,2-a]ピリジン-3-イル)エチニル)-N-フェニルベンズアミド誘導体、その調製法、それを活性成分として含有する癌の予防用又は治療用医薬組成物 |
| US20230301982A1 (en) * | 2020-07-31 | 2023-09-28 | Sun Pharma Advanced Research Company Limited | N'-(2-chloro-6-methylbenzoyl)-4-methyl-3-[2-(3-quinolyl)ethynyl]-benzohydrazide for treatment of alzheimer's disease |
| TW202317530A (zh) | 2021-06-29 | 2023-05-01 | 日商住友化學股份有限公司 | 雜環化合物及含有其之組成物之抗藥性有害節肢動物防除方法 |
| CA3264814A1 (en) | 2022-08-25 | 2024-02-29 | Sun Pharma Advanced Res Co Ltd | METHODS OF TREATMENT OF CHRONIC MYELOID LEUKEMIA USING THE TYROSINE KINASE INHIBITOR VODOBATINIB |
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| US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| EP2308833A3 (en) | 1999-04-15 | 2011-09-28 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| MXPA02010231A (es) * | 2001-11-27 | 2004-12-13 | Warner Lambert Co | Inhibidores aminotransferasa dependientes de aminoacidos de cadena ramificada y su uso en el tratamiento de las enfermedades neurodegenerativas. |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| EP1729771B1 (en) * | 2004-03-22 | 2009-10-14 | Eli Lilly & Company | Pyridyl derivatives and their use as mglu5 receptor antagonists |
| EP1973545B1 (en) * | 2005-12-23 | 2013-01-30 | Ariad Pharmaceuticals, Inc. | Bicyclic heteroaryl compounds |
| CN101389338B (zh) * | 2005-12-23 | 2013-06-26 | 阿里亚德医药股份有限公司 | 双环杂芳基化合物 |
| US7790756B2 (en) | 2006-10-11 | 2010-09-07 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| WO2009100536A1 (en) * | 2008-02-15 | 2009-08-20 | Methylgene Inc. | Inhibitors of kinase activity with 1,2-di-cyclyl substituted alkyne structures |
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| CA2825367A1 (en) | 2012-07-26 |
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| US9024021B2 (en) | 2015-05-05 |
| CN103502217B (zh) | 2015-11-25 |
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| EP2665709B1 (en) | 2016-12-07 |
| BR112013018212B1 (pt) | 2021-12-14 |
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| AU2012208388C1 (en) | 2017-04-27 |
| EA024194B8 (ru) | 2016-11-30 |
| EP2665709A1 (en) | 2013-11-27 |
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