AU2011245441B2 - Activators of human pyruvate kinase - Google Patents
Activators of human pyruvate kinase Download PDFInfo
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- AU2011245441B2 AU2011245441B2 AU2011245441A AU2011245441A AU2011245441B2 AU 2011245441 B2 AU2011245441 B2 AU 2011245441B2 AU 2011245441 A AU2011245441 A AU 2011245441A AU 2011245441 A AU2011245441 A AU 2011245441A AU 2011245441 B2 AU2011245441 B2 AU 2011245441B2
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- Prior art keywords
- oxo
- sulfonamide
- tetrahydroquinoline
- alkyl
- cancer
- 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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- 108020005115 Pyruvate Kinase Proteins 0.000 title abstract description 14
- 102000013009 Pyruvate Kinase Human genes 0.000 title abstract description 13
- 239000012190 activator Substances 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 111
- -1 C 1 -C 4 alkoxyl Chemical group 0.000 claims description 171
- 238000000034 method Methods 0.000 claims description 103
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 229940124530 sulfonamide Drugs 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000004122 cyclic group Chemical group 0.000 claims description 32
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 201000011510 cancer Diseases 0.000 claims description 24
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 230000004913 activation Effects 0.000 claims description 19
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- 125000003545 alkoxy group Chemical group 0.000 claims description 15
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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
- C07D215/16—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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
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| US61/329,158 | 2010-04-29 | ||
| PCT/US2011/033852 WO2011137089A1 (en) | 2010-04-29 | 2011-04-26 | Activators of human pyruvate kinase |
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| EP2417123A2 (en) | 2009-04-06 | 2012-02-15 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| EP2448581B1 (en) | 2009-06-29 | 2016-12-07 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| CA2944788C (en) | 2009-06-29 | 2023-08-22 | Agios Pharmaceuticals, Inc. | Compounds, and compositions thereof, which modulate pyruvate kinase m2, and methods of making same |
| JP5837091B2 (ja) | 2010-12-17 | 2015-12-24 | アジオス ファーマシューティカルズ， インコーポレイテッド | ピルビン酸キナーゼｍ２（ｐｋｍ２）調節剤としての新規ｎ−（４−（アゼチジン−１−カルボニル）フェニル）−（ヘテロ−）アリールスルホンアミド誘導体 |
| JP6092118B2 (ja) * | 2010-12-21 | 2017-03-08 | アジオス ファーマシューティカルズ， インコーポレイテッド | ニ環式ｐｋｍ２活性化剤 |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| KR101873543B1 (ko) | 2011-05-03 | 2018-07-02 | 아지오스 파마슈티컬스 아이엔씨. | 치료에 사용하기 위한 피루베이트 키나아제 활성제 |
| WO2012151440A1 (en) * | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia |
| WO2013027168A1 (en) * | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| WO2013122897A1 (en) | 2012-02-13 | 2013-08-22 | Amgen Inc. | Dihydrobenzoxazine and tetrahydroquinoxaline sodium channel inhibitors |
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| US9458132B2 (en) * | 2012-11-08 | 2016-10-04 | Agios Pharmaceuticals, Inc | Therapeutic compounds and compositions and their use as PKM2 modulators |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| CN105272904B (zh) * | 2014-07-18 | 2019-04-09 | 中国科学院广州生物医药与健康研究院 | N-苯基酰胺类化合物及其应用 |
| DK3174868T3 (da) | 2014-08-01 | 2021-11-08 | Nuevolution As | Forbindelser, der er aktive mod bromodomæner |
| FR3030516B1 (fr) | 2014-12-19 | 2019-12-27 | Galderma Research & Development | Derives sulfonamides bicycles en tant qu'agonistes inverses du recepteur gamma orphelin associe aux retinoides ror gamma (t) |
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| DK3307271T3 (da) | 2015-06-11 | 2023-10-09 | Agios Pharmaceuticals Inc | Fremgangsmåder til anvendelse af pyruvatkinase-aktivatorer |
| US10626087B2 (en) | 2015-07-10 | 2020-04-21 | Loyola University Of Chicago | Indoline and tetrahydroquinoline sulfonyl inhibitors of dimetalloenzymes and use of the same |
| DK3448859T3 (da) | 2017-03-20 | 2019-09-23 | Forma Therapeutics Inc | Pyrrolopyrrolsammensætninger som pyruvatkinase- (pkr) aktivatorer |
| TWI796353B (zh) | 2017-08-15 | 2023-03-21 | 美商阿吉歐斯製藥公司 | 丙酮酸激酶調節劑及其用途 |
| WO2019043208A1 (en) * | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROQUINOLINONES |
| CN112105602A (zh) * | 2018-03-01 | 2020-12-18 | 反应生物公司 | 基于喹啉和异喹啉的hdac抑制剂及其使用方法 |
| GB201810092D0 (en) | 2018-06-20 | 2018-08-08 | Ctxt Pty Ltd | Compounds |
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| JP7450610B2 (ja) | 2018-09-19 | 2024-03-15 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | ピルビン酸キナーゼｒの活性化 |
| FI3986890T3 (fi) | 2019-06-18 | 2024-01-15 | Pfizer | Bentsisoksatsolisulfonamidijohdannaisia |
| MX2022003254A (es) | 2019-09-19 | 2022-04-18 | Forma Therapeutics Inc | Composiciones activadoras de piruvato cinasa r (pkr). |
| DE102019129527A1 (de) | 2019-10-31 | 2021-05-06 | Forschungszentrum Jülich GmbH | Inhibitoren für Bromodomänen |
| US20240000806A1 (en) * | 2020-11-20 | 2024-01-04 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods and materials for inhibiting cb1 activity |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2013525438A (ja) | 2013-06-20 |
| AU2011245441A1 (en) | 2012-11-15 |
| US20150183744A1 (en) | 2015-07-02 |
| WO2011137089A1 (en) | 2011-11-03 |
| EP2563761A1 (en) | 2013-03-06 |
| US20130109672A1 (en) | 2013-05-02 |
| CA2797694A1 (en) | 2011-11-03 |
| US9708267B2 (en) | 2017-07-18 |
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