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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Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2758071C (en) | 2009-04-06 | 2018-01-09 | Agios Pharmaceuticals, Inc. | Pyruvate kinase m2 modulators, therapeutic compositions and related methods of use |
| ES2618630T3 (es) | 2009-06-29 | 2017-06-21 | Agios Pharmaceuticals, Inc. | Composiciones terapéuticas y métodos de uso relacionados |
| TWI598337B (zh) | 2009-06-29 | 2017-09-11 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| WO2012083246A1 (en) | 2010-12-17 | 2012-06-21 | Agios Pharmaceuticals, Inc. | Novel n- (4- (azetidine - 1 - carbonyl) phenyl) - (hetero - ) arylsulfonamide derivatives as pyruvate kinase m2 (pmk2) modulators |
| ES2569712T3 (es) * | 2010-12-21 | 2016-05-12 | Agios Pharmaceuticals, Inc. | Activadores de PKM2 bicíclicos |
| 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 |
| SMT202400081T1 (it) | 2011-05-03 | 2024-03-13 | Agios Pharmaceuticals Inc | Attivatori della piruvato chinasi per uso in terapia |
| US9181231B2 (en) | 2011-05-03 | 2015-11-10 | 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 |
| WO2013134518A1 (en) | 2012-03-09 | 2013-09-12 | Amgen Inc. | Sulfamide sodium channel inhibitors |
| EA032007B1 (ru) * | 2012-11-08 | 2019-03-29 | Аджиос Фармасьютикалз, Инк. | Терапевтические соединения и композиции и их использование в качестве модуляторов пк-m2 |
| 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 |
| JP6759514B2 (ja) | 2014-08-01 | 2020-09-23 | ヌエヴォリューション・アクティーゼルスカブＮｕｅｖｏｌｕｔｉｏｎ Ａ／Ｓ | ブロモドメインに対して活性な化合物 |
| FR3030518B1 (fr) | 2014-12-19 | 2018-03-23 | Galderma Research & Development | Derives sulfonamides en tant qu'agonistes inverses du recepteur gamma orphelin associe aux retinoides ror gamma (t) |
| 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) |
| CA2989111C (en) | 2015-06-11 | 2023-10-03 | Agios Pharmaceuticals, Inc. | Methods of using pyruvate kinase activators |
| WO2017011408A1 (en) * | 2015-07-10 | 2017-01-19 | Loyola University Of Chicago | Indoline and tetrahydroquinoline sulfonyl inhibitors of dimetalloenzymes and use of the same |
| LT3483164T (lt) | 2017-03-20 | 2020-05-11 | Forma Therapeutics, Inc. | Pirolpirolo kompozicijos kaip piruvato kinazės (pkr) aktyvatoriai |
| 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 |
| GB201810581D0 (en) | 2018-06-28 | 2018-08-15 | Ctxt Pty Ltd | Compounds |
| EP3853206B1 (en) | 2018-09-19 | 2024-04-10 | Novo Nordisk Health Care AG | Treating sickle cell disease with a pyruvate kinase r activating compound |
| EP3852791B1 (en) | 2018-09-19 | 2024-07-03 | Novo Nordisk Health Care AG | Activating pyruvate kinase r |
| DK4299135T3 (da) | 2019-06-18 | 2025-09-08 | Pfizer | Benzisoxazol-sulfonamid-derivater |
| HRP20251148T1 (hr) | 2019-09-19 | 2025-11-21 | Novo Nordisk Health Care Ag | Pripravci koji aktiviraju piruvat-kinazu r (pkr) |
| DE102019129527A1 (de) | 2019-10-31 | 2021-05-06 | Forschungszentrum Jülich GmbH | Inhibitoren für Bromodomänen |
| WO2022109292A1 (en) * | 2020-11-20 | 2022-05-27 | 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010042867A2 (en) * | 2008-10-09 | 2010-04-15 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Activators of human pyruvate kinase |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL80628C (https=) * | 1949-07-23 | |||
| US3998828A (en) | 1975-01-31 | 1976-12-21 | Pfizer Inc. | 4-[2-(1,3-Dialkyl-1,2,3,4-tetra-hydropyrimidine-2,4-dione-5-carboxamido)ethyl]-1-piperidine sulfonamide |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| JPS569749A (en) * | 1979-07-04 | 1981-01-31 | Mitsubishi Paper Mills Ltd | Preparation of lithographic plate |
| DE2948434A1 (de) | 1979-12-01 | 1981-06-11 | Hoechst Ag, 6000 Frankfurt | 1-piperidinsulfonylharnstoffe und verfahren zu ihrer herstellung |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US4593102A (en) | 1984-04-10 | 1986-06-03 | A. H. Robins Company, Inc. | N-[(amino)alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulfur linked substitution in the 2, 3 or 4-position |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| JPH0667926B2 (ja) | 1985-11-12 | 1994-08-31 | 旭化成工業株式会社 | 環状のイソキノリンスルホンアミド誘導体 |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5962490A (en) | 1987-09-25 | 1999-10-05 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| BR9200951A (pt) | 1991-03-21 | 1992-11-17 | Hoffmann La Roche | Compostos, processo para sua producao,preparacoes farmaceuticas e uso |
| IT1252567B (it) | 1991-12-20 | 1995-06-19 | Italfarmaco Spa | Derivati di 5-isochinolinsolfonammidi inibitori delle protein-chinasi |
| US5891435A (en) | 1993-04-16 | 1999-04-06 | Research Corporation Technologies, Inc. | Methods and compositions for delaying or preventing the onset of autoimmune disease |
| US5639600A (en) | 1994-08-05 | 1997-06-17 | The Regents Of The University Of California | Diagnosis and treatment of cell proliferative disease having clonal macrophage involvement |
| CA2210889C (en) | 1995-01-20 | 2007-08-28 | G.D. Searle & Co. | Bis-sulfonamide hydroxyethylamino retroviral protease inhibitors |
| JPH09286783A (ja) * | 1996-02-19 | 1997-11-04 | Fuji Photo Film Co Ltd | 感熱記録材料及びジアゾ化合物 |
| DE19629335A1 (de) | 1996-07-20 | 1998-01-22 | Golden Records Ass Internation | Karte aus Kunststoff |
| US6020357A (en) | 1996-12-23 | 2000-02-01 | Dupont Pharmaceuticals Company | Nitrogen containing heteroaromatics as factor Xa inhibitors |
| AR016384A1 (es) | 1997-07-30 | 2001-07-04 | Smithkline Beecham Corp | Inhibidores de caspasas, composiciones farmaceuticas que comprenden dichos inhibidores de caspasas y uso de los inhibidores de caspasas para prepararun medicamento util para el tratamiento de apoptosis y desordenes asociados con excesiva actividad de la convertosa il-1 beta. |
| AR016551A1 (es) * | 1997-07-30 | 2001-07-25 | Smithkline Beecham Corp | Derivados de 2-oxindol, composiciones farmaceuticas que los comprenden y el uso de los mismos para la manufactura de medicamentos |
| US7087648B1 (en) | 1997-10-27 | 2006-08-08 | The Regents Of The University Of California | Methods for modulating macrophage proliferation using polyamine analogs |
| DE19755268A1 (de) * | 1997-12-12 | 1999-06-17 | Merck Patent Gmbh | Benzamidinderivate |
| US6617171B2 (en) | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
| KR20010098982A (ko) | 1999-02-09 | 2001-11-08 | 3-디멘져널 파마슈티칼즈 인코오포레이티드 | 프로테아제 억제제로서의 헤테로아릴 아미딘, 메틸아미딘및 구아니딘 |
| US6211182B1 (en) | 1999-03-08 | 2001-04-03 | Schering Corporation | Imidazole compounds substituted with a six or seven membered heterocyclic ring containing two nitrogen atoms |
| CO5170498A1 (es) * | 1999-05-28 | 2002-06-27 | Abbott Lab | Biaril sulfonamidas son utiles como inhibidores de proliferacion celular |
| JP2003510278A (ja) | 1999-09-30 | 2003-03-18 | スミスクライン・ビーチャム・コーポレイション | カスパーゼおよびアポプトシス |
| JP2003535847A (ja) * | 2000-06-02 | 2003-12-02 | スージェン・インコーポレーテッド | 蛋白質キナーゼ／ホスファターゼ阻害剤としてのインドリノン誘導体 |
| AR032885A1 (es) | 2000-08-16 | 2003-12-03 | Actelion Pharmaceuticals Ltd | Bis-sulfonamidas, composiciones farmaceuticas, procedimiento para prepararlas y el uso de las mismas para la produccion de las composiciones farmaceuticas |
| AU2002319180B2 (en) | 2001-05-23 | 2007-07-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Pyruvate-kinase as a novel target molecule |
| CA2479932A1 (en) | 2002-03-28 | 2003-10-09 | Eli Lilly And Company | Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders |
| WO2003099811A1 (en) * | 2002-05-23 | 2003-12-04 | Cytopia Pty Ltd | Kinase inhibitors |
| EP2436676A1 (en) | 2002-06-12 | 2012-04-04 | Symphony Evolution, Inc. | Human adam-10 inhibitors |
| GB0215650D0 (en) * | 2002-07-05 | 2002-08-14 | Cyclacel Ltd | Bisarylsufonamide compounds |
| WO2004076640A2 (en) | 2003-02-25 | 2004-09-10 | Ambion, Inc. | Small-molecule inhibitors of angiogenin and rnases and in vivo and in vitro methods of using same |
| JP2005008624A (ja) * | 2003-05-27 | 2005-01-13 | Taiho Yakuhin Kogyo Kk | テトラハイドロキノリン骨格を有するスルホンアミド誘導体およびその塩 |
| WO2005074946A1 (en) | 2004-02-10 | 2005-08-18 | Adenobio N.V. | Stable and active complexes of adenosine and adenosine phosphates with aminoalcohols for the treatment of pulmonary artery hypertension, cardiac failure and other diseases |
| CA2556589A1 (en) | 2004-02-24 | 2005-09-01 | Bioaxone Therapeutique Inc. | 4-substituted piperidine derivatives |
| RU2261246C1 (ru) | 2004-04-15 | 2005-09-27 | Общество с ограниченной ответственностью "Исследовательский Институт Химического Разнообразия" (ООО "Исследовательский Институт Химического Разнообразия") | Замещенные 7-сульфонил бензо[b][1,4]диазепины (варианты), способы их получения (варианты), фокусированная библиотека и фармацевтическая композиция |
| DE102004028862A1 (de) * | 2004-06-15 | 2005-12-29 | Merck Patent Gmbh | 3-Aminoindazole |
| EP1773310B9 (en) | 2004-06-24 | 2012-04-25 | Temple University - Of The Commonwealth System of Higher Education | Alpha, beta-unsaturated sulfones, sulfoxides, sulfonimides, sulfinimides, acylsulfonamides and acylsulfinamides and therapeutic uses thereof |
| TW200606152A (en) | 2004-07-02 | 2006-02-16 | Tanabe Seiyaku Co | Piperidine compound and process for preparing the same |
| FR2872704B1 (fr) | 2004-07-12 | 2007-11-02 | Laurent Schwartz | Pluritherapie contre le cancer |
| WO2006055880A2 (en) | 2004-11-16 | 2006-05-26 | Genzyme Corporation | Diagnostic pkm2 methods and compositions |
| JP4058106B2 (ja) | 2005-02-18 | 2008-03-05 | アストラゼネカ アクチボラグ | 抗菌性のピペリジン誘導体 |
| CA2608599A1 (en) | 2005-05-16 | 2006-11-23 | Vertex Pharmaceuticals Incorporated | Bicyclic derivatives as modulators of ion channels |
| AR054363A1 (es) | 2005-05-23 | 2007-06-20 | Astrazeneca Ab | Compuestos que exhiben actividad moduladora en el receptor 5-hidroxi-triptamina 6 |
| FR2887881B1 (fr) * | 2005-07-01 | 2009-10-09 | Pierre Fabre Medicament Sa | Inhibiteurs de proteines kinases |
| DK1910384T3 (da) * | 2005-08-04 | 2012-12-17 | Sirtris Pharmaceuticals Inc | Imidazo [2,1-b] thiazol-derivater som sirtuinmodulerende forbindelser |
| WO2007076055A2 (en) * | 2005-12-22 | 2007-07-05 | Entremed, Inc. | Compositions and methods comprising proteinase activated receptor antagonists |
| EP1962851A2 (en) | 2005-12-22 | 2008-09-03 | SmithKline Beecham Corporation | Compounds |
| JP2009521444A (ja) | 2005-12-22 | 2009-06-04 | メルク エンド カムパニー インコーポレーテッド | カルシウムチャンネルブロッカーとなる置換ピペリジン |
| CN101404987A (zh) | 2006-01-20 | 2009-04-08 | 史密丝克莱恩比彻姆公司 | 磺酰胺衍生物在治疗代射和神经系统疾病中的用途 |
| WO2007117699A2 (en) * | 2006-04-07 | 2007-10-18 | University Of South Florida | Inhibition of shp2/ptpn11 protein tyrosine phosphatase by nsc-87877, nsc-117199 and their analogs |
| US20090325944A1 (en) * | 2006-04-12 | 2009-12-31 | Suzanne Walker Kahne | Methods and Compositions for Modulating Glycosylation |
| EP1878723B1 (fr) | 2006-07-11 | 2010-05-26 | Sanofi-Aventis | Dérivés de N-[(1,5-diphényl-1H-pyrazol-3-yl)méthyl]sulfonamide antagonistes des récepteurs CB1 des cannabinoïdes |
| TW200817319A (en) * | 2006-08-10 | 2008-04-16 | Astellas Pharma Inc | Sulfonamide compound or salt thereof |
| CL2007003223A1 (es) | 2006-11-10 | 2008-01-11 | Wyeth Corp | Compuestos derivados de piperidinil 4-arilsulfonamidas n-sustituidas, que actuan como moduladores de la proteina sfrp-1; proceso para preparar los compuestos; co mposicion farmaceutica que comprende a dichos copmpuestos y uso de los compuestos para preparar medicamentos para el tratamiento de enfermedades. |
| JP2010520268A (ja) | 2007-03-05 | 2010-06-10 | バイオリポックス・アーベー | 炎症の治療に有用な新しいメチレンビスフェニル化合物 |
| WO2008124838A1 (en) * | 2007-04-10 | 2008-10-16 | University Of Maryland, Baltimore | Compounds that inhibit human dna ligases and methods of treating cancer |
| US7897776B2 (en) | 2007-04-23 | 2011-03-01 | Salutria Pharmaceuticals Llc | Sulfonamide containing compounds for treatment of inflammatory disorders |
| WO2009025781A1 (en) | 2007-08-16 | 2009-02-26 | Beth Israel Deaconess Medical Center | Activators of pyruvate kinase m2 and methods of treating disease |
| EP2195656A4 (en) * | 2007-08-21 | 2011-10-19 | Senomyx Inc | HUMAN T2R BITTERITY RECEPTORS AND USES THEREOF |
| US20110105477A1 (en) * | 2007-09-14 | 2011-05-05 | The Regents Of The University Of Michigan | Compositions and methods relating to hiv protease inhibition |
| EP2211615A4 (en) * | 2007-10-22 | 2010-10-13 | Glaxosmithkline Llc | PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| WO2009084501A1 (ja) * | 2007-12-27 | 2009-07-09 | Asahi Kasei Pharma Corporation | スルタム誘導体 |
| GB0815947D0 (en) * | 2008-09-02 | 2008-10-08 | Univ Dundee | Compounds |
| EP3103452A1 (en) * | 2009-08-25 | 2016-12-14 | Abraxis BioScience, LLC | Combination therapy with nanoparticle compositions of taxane and hedgehog inhibitors |
| WO2011153359A1 (en) | 2010-06-04 | 2011-12-08 | Albany Molecular Research, Inc. | Glycine transporter-1 inhibitors, methods of making them, and uses thereof |
-
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- 2011-04-26 US US13/643,594 patent/US20130109672A1/en not_active Abandoned
- 2011-04-26 JP JP2013508139A patent/JP2013525438A/ja active Pending
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- 2011-04-26 WO PCT/US2011/033852 patent/WO2011137089A1/en not_active Ceased
- 2011-04-26 EP EP11730473A patent/EP2563761A1/en not_active Withdrawn
-
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- 2015-03-10 US US14/643,107 patent/US9708267B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010042867A2 (en) * | 2008-10-09 | 2010-04-15 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Activators of human pyruvate kinase |
Non-Patent Citations (1)
| Title |
|---|
| Boxer, M. B. et al, "Identification of activators for the M2 isoform of human pyruvate kinase Version 3", Molecular Libraries, 2009, pages 1-25. Retrieved from internet: http://www.ncbi.nlm.nih.gov/books/NBK56225/pdf/ml170.pdf * |
Also Published As
| Publication number | Publication date |
|---|---|
| US20130109672A1 (en) | 2013-05-02 |
| AU2011245441A1 (en) | 2012-11-15 |
| EP2563761A1 (en) | 2013-03-06 |
| US9708267B2 (en) | 2017-07-18 |
| CA2797694A1 (en) | 2011-11-03 |
| JP2013525438A (ja) | 2013-06-20 |
| WO2011137089A1 (en) | 2011-11-03 |
| US20150183744A1 (en) | 2015-07-02 |
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