ES2769648T3 - Nuevos compuestos como inhibidores duales de histona metiltransferasas y ADN metiltransferasasASAS - Google Patents
Nuevos compuestos como inhibidores duales de histona metiltransferasas y ADN metiltransferasasASAS Download PDFInfo
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- ES2769648T3 ES2769648T3 ES15714185T ES15714185T ES2769648T3 ES 2769648 T3 ES2769648 T3 ES 2769648T3 ES 15714185 T ES15714185 T ES 15714185T ES 15714185 T ES15714185 T ES 15714185T ES 2769648 T3 ES2769648 T3 ES 2769648T3
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- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims abstract description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 52
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- 125000004122 cyclic group Chemical group 0.000 claims abstract description 35
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 25
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 24
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- BMEVVKJXVKFHJE-UHFFFAOYSA-N 1-amino-3-[[2-(3,4-dichlorophenyl)-7-methoxyquinolin-4-yl]amino]propan-2-ol;hydrochloride Chemical compound Cl.N=1C2=CC(OC)=CC=C2C(NCC(O)CN)=CC=1C1=CC=C(Cl)C(Cl)=C1 BMEVVKJXVKFHJE-UHFFFAOYSA-N 0.000 claims 1
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- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- LEWDKQKVAFOMPI-UHFFFAOYSA-N quinoline-4-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=NC2=C1 LEWDKQKVAFOMPI-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 230000009467 reduction Effects 0.000 description 1
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- 230000002441 reversible effect Effects 0.000 description 1
- 229940120975 revlimid Drugs 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000005402 stannate group Chemical group 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 238000011222 transcriptome analysis Methods 0.000 description 1
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- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D215/16—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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- 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
- C07D401/02—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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/02—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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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| EP14382230 | 2014-06-16 | ||
| PCT/EP2015/056860 WO2015192981A1 (en) | 2014-06-16 | 2015-03-30 | Novel compounds as dual inhibitors of histone methyltransferases and dna methyltransferases |
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| ES2769648T3 true ES2769648T3 (es) | 2020-06-26 |
Family
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| EP (1) | EP3154957B1 (OSRAM) |
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| AU (1) | AU2015276537B2 (OSRAM) |
| CA (1) | CA2987978C (OSRAM) |
| DK (1) | DK3154957T3 (OSRAM) |
| ES (1) | ES2769648T3 (OSRAM) |
| WO (1) | WO2015192981A1 (OSRAM) |
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| WO2017102677A1 (en) * | 2015-12-14 | 2017-06-22 | Fundación Para La Investigación Médica Aplicada | 2,4,6,7-tetrasubstituted quinoline compounds as inhibitors of dna methyltransferases |
| KR20230130747A (ko) * | 2016-04-15 | 2023-09-12 | 에피자임, 인코포레이티드 | Ehmt1 및 ehmt2 저해제로서의 아민-치환된 아릴 또는 헤테로아릴 화합물 |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| US11278550B2 (en) | 2016-05-17 | 2022-03-22 | Duke University | Compositions and methods for the treatment of Prader-Willi syndrome |
| US11433068B2 (en) * | 2016-09-08 | 2022-09-06 | The General Hospital Corporation | Treatment of cancers having alterations within the SWI/SNF chromatin remodeling complex |
| EP4063358B1 (en) * | 2016-12-22 | 2024-05-22 | Global Blood Therapeutics, Inc. | Histone methyltransferase inhibitors |
| WO2018119065A1 (en) | 2016-12-22 | 2018-06-28 | Asddr, Llc | Use of histone methyltransferase inhibitors and histone deacetylase inhibitors for therapy of phelan-mcdermid syndrome |
| US20200113901A1 (en) * | 2017-03-31 | 2020-04-16 | Epizyme, Inc. | Methods of using ehmt2 inhibitors |
| EP3612181A4 (en) | 2017-04-21 | 2021-01-06 | Epizyme, Inc. | Combination therapies with ehmt2 inhibitors |
| BR112019025770A2 (pt) | 2017-06-09 | 2020-06-23 | Global Blood Therapeutics, Inc. | Compostos de azaindol como inibidores de histona metiltransferase |
| WO2018229139A1 (en) | 2017-06-14 | 2018-12-20 | Fundación Para La Investigación Médica Aplicada | Novel compounds for use in cancer |
| WO2019036384A1 (en) | 2017-08-15 | 2019-02-21 | Global Blood Therapeutics, Inc. | TRICYCLIC COMPOUNDS AS HISTONE INHIBITORS METHYLTRANSFERASES |
| EP3668863B1 (en) | 2017-08-15 | 2025-03-19 | Global Blood Therapeutics, Inc. | Tricyclic compounds as histone methyl-transferase inhibitors |
| SG11202003225YA (en) * | 2017-10-18 | 2020-05-28 | Epizyme Inc | Amine-substituted heterocyclic compounds as ehmt2 inhibitors, salts thereof, and methods of synthesis thereof |
| WO2019079607A1 (en) * | 2017-10-18 | 2019-04-25 | Epizyme, Inc. | METHODS OF USING EHMT2 INHIBITORS IN THE TREATMENT OR PREVENTION OF BLOOD DISORDERS |
| EP3807248A4 (en) * | 2018-05-29 | 2021-10-27 | Council of Scientific and Industrial Research | BICYCLIC TOPOISOMERASE I INHIBITOR COMPOUNDS, THEIR PREPARATION AND USE |
| WO2019243236A1 (en) | 2018-06-18 | 2019-12-26 | Fundación Para La Investigación Médica Aplicada | New anticancer drug combinations |
| CN112390791B (zh) * | 2019-08-14 | 2023-08-01 | 复旦大学 | 一类dna甲基转移酶1荧光探针及其用途 |
| JP2023536634A (ja) * | 2020-08-07 | 2023-08-28 | アトス セラピューティクス，インコーポレイテッド | 自己免疫疾患および癌の処置のための小分子 |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
| CN115160294B (zh) * | 2022-06-27 | 2023-09-29 | 中山大学 | 一种G9a/GLP共价抑制剂及其制备方法及应用 |
| CN120965666A (zh) * | 2025-10-21 | 2025-11-18 | 四川大学华西医院 | 一种喹啉类化合物、制备方法和用途及其药物组合物 |
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| WO1999001154A1 (en) * | 1997-07-03 | 1999-01-14 | University Of Iowa Research Foundation | Method for inhibiting immunostimulatory dna associated responses |
| CA2412345A1 (en) * | 1999-06-16 | 2000-12-21 | University Of Iowa Research Foundation | Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases |
| EP1088818B1 (en) | 1999-10-01 | 2004-11-03 | F. Hoffmann-La Roche Ag | Quinolin-4-yl derivatives |
| US6440995B1 (en) * | 1999-10-01 | 2002-08-27 | Hoffman-La Roche Inc. | Quinolin-4-yl derivatives |
| AU2002361846A1 (en) * | 2001-12-21 | 2003-07-15 | Bayer Pharmaceuticals Corporation | Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
| WO2004056352A1 (en) * | 2002-12-19 | 2004-07-08 | Scios, Inc. | TREATMENT OF OBESITY AND ASSOCIATED CONDITIONS WITH TGF-β INHIBITORS |
| US7314939B2 (en) * | 2003-06-17 | 2008-01-01 | Millennium Pharmaceuticals, Inc. | Compositions and methods for inhibiting TGF-β |
| CA2664631A1 (en) | 2006-10-12 | 2008-04-17 | David J. Bearss | Quinoline derivatives for modulating dna methylation |
| CN101535295A (zh) * | 2006-10-12 | 2009-09-16 | 休普基因公司 | 用于调节dna甲基化的喹啉衍生物 |
| US7790746B2 (en) | 2007-10-12 | 2010-09-07 | Supergen, Inc. | Quinoline derivatives for modulating DNA methylation |
| WO2010151791A1 (en) * | 2009-06-25 | 2010-12-29 | Amgen Inc. | Heterocyclic compounds and their uses |
| CA2770753C (en) * | 2009-08-12 | 2019-01-15 | Kyoto University | Method for inducing differentiation of pluripotent stem cells into neural precursor cells |
| WO2011054433A1 (en) * | 2009-11-07 | 2011-05-12 | Merck Patent Gmbh | Heteroarylaminoquinolines as tgf-beta receptor kinase inhibitors |
| EP2771012A4 (en) * | 2011-10-24 | 2015-06-24 | Glaxosmithkline Ip No 2 Ltd | NEW CONNECTIONS |
| EP2828250B1 (en) | 2012-03-19 | 2021-03-10 | Imperial College Innovations Limited | Quinazoline compounds and their use in therapy |
| EP2730558A1 (en) | 2012-11-08 | 2014-05-14 | Ikerchem, S.L. | Indole derivatives, pharmaceutical compositions containing such indoles and their use as DNA methylation modulators |
| EP2918014B1 (en) * | 2012-11-09 | 2018-10-31 | OCT Circuit Technologies International Limited | Analog to digital conversion method with offset tracking and correction and analog to digital converter implementing the same |
| JP6338601B2 (ja) * | 2013-03-01 | 2018-06-06 | フンダシオン パラ ラ インベスティガシオン メディカ アプリカダ | ホスホジエステラーゼとヒストンデアセチラーゼの二重阻害剤としての新規な化合物 |
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2015
- 2015-03-30 US US15/315,326 patent/US9840500B2/en active Active
- 2015-03-30 CN CN201580034131.4A patent/CN106536509B/zh active Active
- 2015-03-30 ES ES15714185T patent/ES2769648T3/es active Active
- 2015-03-30 WO PCT/EP2015/056860 patent/WO2015192981A1/en not_active Ceased
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- 2015-03-30 JP JP2016573017A patent/JP6527534B2/ja active Active
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- 2015-03-30 EP EP15714185.4A patent/EP3154957B1/en active Active
- 2015-03-30 CA CA2987978A patent/CA2987978C/en active Active
Also Published As
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| AU2015276537A1 (en) | 2017-01-05 |
| CN106536509B (zh) | 2020-06-09 |
| CN106536509A (zh) | 2017-03-22 |
| CA2987978C (en) | 2022-08-16 |
| AU2015276537B2 (en) | 2019-03-14 |
| US20170121316A1 (en) | 2017-05-04 |
| WO2015192981A1 (en) | 2015-12-23 |
| US9840500B2 (en) | 2017-12-12 |
| JP2017524668A (ja) | 2017-08-31 |
| CA2987978A1 (en) | 2015-12-23 |
| EP3154957B1 (en) | 2019-11-20 |
| EP3154957A1 (en) | 2017-04-19 |
| JP6527534B2 (ja) | 2019-06-05 |
| DK3154957T3 (da) | 2020-02-17 |
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