AU2015276537B2 - Novel compounds as dual inhibitors of histone methyltransferases and dna methyltransferases - Google Patents
Novel compounds as dual inhibitors of histone methyltransferases and dna methyltransferases Download PDFInfo
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- AU2015276537B2 AU2015276537B2 AU2015276537A AU2015276537A AU2015276537B2 AU 2015276537 B2 AU2015276537 B2 AU 2015276537B2 AU 2015276537 A AU2015276537 A AU 2015276537A AU 2015276537 A AU2015276537 A AU 2015276537A AU 2015276537 B2 AU2015276537 B2 AU 2015276537B2
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- amino
- methoxy
- quinolyl
- phenyl
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- 108010036115 Histone Methyltransferases Proteins 0.000 title claims description 23
- 102000011787 Histone Methyltransferases Human genes 0.000 title claims description 23
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
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- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 102100036279 DNA (cytosine-5)-methyltransferase 1 Human genes 0.000 claims description 44
- 125000004122 cyclic group Chemical group 0.000 claims description 40
- 108010009540 DNA (Cytosine-5-)-Methyltransferase 1 Proteins 0.000 claims description 34
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 31
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- 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
-
- 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
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- 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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
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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 |
Citations (3)
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| EP1088818A1 (en) * | 1999-10-01 | 2001-04-04 | F. Hoffmann-La Roche Ag | Quinolin-4-yl derivatives |
| WO2003055866A1 (en) * | 2001-12-21 | 2003-07-10 | Bayer Pharmaceuticals Corporation | Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
| WO2011054433A1 (en) * | 2009-11-07 | 2011-05-12 | Merck Patent Gmbh | Heteroarylaminoquinolines as tgf-beta receptor kinase inhibitors |
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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 |
| US6440995B1 (en) * | 1999-10-01 | 2002-08-27 | Hoffman-La Roche Inc. | Quinolin-4-yl derivatives |
| 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 |
| 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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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1088818A1 (en) * | 1999-10-01 | 2001-04-04 | F. Hoffmann-La Roche Ag | Quinolin-4-yl derivatives |
| WO2003055866A1 (en) * | 2001-12-21 | 2003-07-10 | Bayer Pharmaceuticals Corporation | Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
| WO2011054433A1 (en) * | 2009-11-07 | 2011-05-12 | Merck Patent Gmbh | Heteroarylaminoquinolines as tgf-beta receptor kinase inhibitors |
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| AU2015276537A1 (en) | 2017-01-05 |
| CN106536509B (zh) | 2020-06-09 |
| CN106536509A (zh) | 2017-03-22 |
| CA2987978C (en) | 2022-08-16 |
| 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 |
| ES2769648T3 (es) | 2020-06-26 |
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