CN106977495B - Dna-pk抑制剂 - Google Patents

Dna-pk抑制剂 Download PDF

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CN106977495B
CN106977495B CN201710185886.5A CN201710185886A CN106977495B CN 106977495 B CN106977495 B CN 106977495B CN 201710185886 A CN201710185886 A CN 201710185886A CN 106977495 B CN106977495 B CN 106977495B
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radical
group
ring
atoms
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CN106977495A (zh
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P·S·查里夫森
K·M·科特雷尔
邓红波
J·P·达菲
高淮
S·吉鲁
J·格林
K·L·杰克逊
J·P·马克斯韦尔
M·A·莫里斯
A·C·皮尔斯
N·D·瓦尔
J·M·肯尼迪
D·J·劳弗
M·W·莱德波尔
李磐
徐金旺
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
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    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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Families Citing this family (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY170941A (en) 2011-04-08 2019-09-19 Janssen Sciences Ireland Uc Pyrimidine derivatives for the treatment of viral infections
IN2014MN00862A (OSRAM) 2011-11-09 2015-04-17 Janssen R & D Ireland
US9034885B2 (en) 2012-01-13 2015-05-19 Acea Biosciences Inc. EGFR modulators and uses thereof
EP2841428B1 (en) 2012-04-24 2018-08-22 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
AU2013288600B2 (en) 2012-07-13 2017-06-29 Janssen Sciences Ireland Uc Macrocyclic purines for the treatment of viral infections
MX365114B (es) 2012-10-10 2019-05-23 Janssen Sciences Ireland Uc Derivados pirrolo[3,2-d]pirimidinicos para el tratamiento de infecciones viricas y otras enfermedades.
MY171115A (en) 2012-11-16 2019-09-26 Janssen Sciences Ireland Uc Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections
UA118751C2 (uk) 2013-02-21 2019-03-11 ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі Похідні 2-амінопіримідину для лікування вірусних інфекцій
WO2014159690A1 (en) 2013-03-12 2014-10-02 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
ES2625456T3 (es) 2013-03-29 2017-07-19 Janssen Sciences Ireland Uc Desazapurinonas macrocíclicas para el tratamiento de infecciones víricas
JP6377139B2 (ja) 2013-05-24 2018-08-22 ヤンセン・サイエンシズ・アイルランド・ユーシー ウイルス感染症およびさらなる疾患の処置のためのピリドン誘導体
PL3030563T3 (pl) 2013-06-27 2018-01-31 Janssen Sciences Ireland Uc Pochodne pirolo [3,2-d] pirymidyny do leczenia zakażeń wirusowych i innych chorób
EP3027624B1 (en) 2013-07-30 2018-09-12 Janssen Sciences Ireland UC Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections
RS57306B1 (sr) * 2013-10-17 2018-08-31 Vertex Pharma Inhibitori dnk-pk
PL3424920T3 (pl) * 2013-10-17 2020-11-16 Vertex Pharmaceuticals Incorporated Kokryształy (S)-N-metylo-8-(1-((2'-metylo-4’,6'-dideutero-[4,5'-bipirymidyn]-6-ylo)amino)propan-2-ylo)chinolino-4-karboksyamidu i ich deuterowane pochodne jako inhibitory DNA-PK
US10287268B2 (en) * 2014-07-21 2019-05-14 Dana-Farber Cancer Institute, Inc. Imidazolyl kinase inhibitors and uses thereof
WO2016066115A1 (zh) * 2014-10-31 2016-05-06 厦门大学 取代杂环衍生物、其制备方法和用途
CN104356082B (zh) * 2014-10-31 2016-07-13 厦门大学 一类取代杂环衍生物及其制备方法
CN104352488B (zh) * 2014-10-31 2016-08-31 厦门大学 一类取代杂环衍生物在制备治疗疼痛药物中的应用
WO2017059702A1 (en) * 2015-10-09 2017-04-13 Acea Biosciences, Inc Pharmaceutical salts, physical forms, and compositions of pyrrolopyrimidine kinase inhibitors, and methods of making same
EP3365334B1 (en) * 2015-10-21 2024-07-17 Otsuka Pharmaceutical Co., Ltd. Benzolactam compounds as protein kinase inhibitors
CR20180323A (es) 2015-11-20 2018-08-06 Idorsia Pharmaceuticals Ltd Derivados de indol n-sustituídos como moduladores de los receptores de pge2
CN108697709A (zh) 2015-12-10 2018-10-23 Ptc医疗公司 用于治疗亨廷顿病的方法
SG11201811448RA (en) 2016-07-01 2019-01-30 Janssen Sciences Ireland Unlimited Co Dihydropyranopyrimidines for the treatment of viral infections
US10954242B2 (en) 2016-07-05 2021-03-23 The Broad Institute, Inc. Bicyclic urea kinase inhibitors and uses thereof
CA3030783A1 (en) * 2016-07-13 2018-01-18 Vertex Pharmaceuticals Incorporated Methods, compositions and kits for increasing genome editing efficiency
WO2018053373A1 (en) 2016-09-16 2018-03-22 The General Hospital Corporation Uses of satl-inducible kinase (sik) inhibitors for treating osteoporosis
WO2018064092A1 (en) * 2016-09-27 2018-04-05 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of dna-damaging agents and dna-pk inhibitors
EA038646B1 (ru) 2016-09-29 2021-09-28 Янссен Сайенсиз Айрлэнд Анлимитед Компани Пиримидиновые пролекарства для лечения вирусных инфекций и других заболеваний
AU2017384134B2 (en) * 2016-12-19 2022-03-24 Merck Patent Gmbh Combination of a protein kinase inhibitor and an additional chemotherapeutic agent
CN111163771B (zh) 2017-02-28 2023-07-14 通用医疗公司 嘧啶并嘧啶酮类作为sik抑制剂的用途
WO2018183868A1 (en) * 2017-03-31 2018-10-04 Bioventures, Llc Inhibitors of dna pk and uses thereof
JP2020516682A (ja) 2017-04-07 2020-06-11 エイシア セラピューティクス， インコーポレイテッド ピロロピリミジンキナーゼの薬学的な塩、物理的形態および組成物、ならびにその作製方法
AU2018268311B2 (en) 2017-05-18 2022-02-10 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives as PGE2 receptor modulators
EP3625224B1 (en) 2017-05-18 2021-08-04 Idorsia Pharmaceuticals Ltd N-substituted indole derivatives
US11325899B2 (en) 2017-05-18 2022-05-10 Idorsia Pharmaceuticals Ltd Benzofurane and benzothiophene derivatives as PGE2 receptor modulators
WO2018210992A1 (en) 2017-05-18 2018-11-22 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives
WO2018210994A1 (en) * 2017-05-18 2018-11-22 Idorsia Pharmaceuticals Ltd Phenyl derivatives as pge2 receptor modulators
AU2018282154B2 (en) 2017-06-05 2022-04-07 Ptc Therapeutics, Inc. Compounds for treating huntington's disease
CN111182898B (zh) 2017-06-28 2024-04-16 Ptc医疗公司 用于治疗亨廷顿氏病的方法
WO2019005993A1 (en) 2017-06-28 2019-01-03 Ptc Therapeutics, Inc. METHODS OF TREATING HUNTINGTON'S DISEASE
CN111741955B (zh) 2018-01-17 2024-02-23 沃泰克斯药物股份有限公司 Dna-pk抑制剂
JP7483612B2 (ja) 2018-01-17 2024-05-15 バーテックス ファーマシューティカルズ インコーポレイテッド ゲノム編集効率を増加するためのキノキサリノン化合物、組成物、方法、およびキット
EP3740480B1 (en) 2018-01-17 2024-03-06 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
TW202415645A (zh) 2018-03-01 2024-04-16 愛爾蘭商健生科學愛爾蘭無限公司 ２，４－二胺基喹唑啉衍生物及其醫學用途
WO2019183245A1 (en) 2018-03-20 2019-09-26 Icahn School Of Medicine At Mount Sinai Kinase inhibitor compounds and compositions and methods of use
BR112020019373A2 (pt) 2018-03-27 2020-12-29 Ptc Therapeutics, Inc. Compostos para o tratamento da doença de hutington
EP3814360B8 (en) 2018-06-27 2024-11-06 PTC Therapeutics, Inc. Heteroaryl compounds for treating huntington's disease
IL279688B2 (en) * 2018-06-27 2025-01-01 Ptc Therapeutics Inc Heterocyclic and heteroaryl compounds for the treatment of Huntington's disease
WO2020005877A1 (en) 2018-06-27 2020-01-02 Ptc Therapeutics, Inc. Heteroaryl compounds for treating huntington's disease
EP3906028A4 (en) * 2018-12-31 2022-10-12 Icahn School of Medicine at Mount Sinai KINA INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE
CN111909144A (zh) * 2019-05-10 2020-11-10 山东轩竹医药科技有限公司 喹唑啉类dna-pk抑制剂
JP7696834B2 (ja) * 2019-05-27 2025-06-23 ディザル（ジァンスー）ファーマシューティカル・カンパニー・リミテッド Ｄｎａ依存性タンパク質キナーゼ阻害剤
WO2020257325A1 (en) 2019-06-17 2020-12-24 Vertex Pharmaceuticals Inc. Compositions and methods for editing beta-globin for treatment of hemaglobinopathies
CN112300126A (zh) * 2019-07-31 2021-02-02 山东轩竹医药科技有限公司 杂环类dna-pk抑制剂
AU2020337919A1 (en) 2019-08-27 2022-03-24 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of disorders associated with repetitive DNA
CA3150516A1 (en) 2019-09-11 2021-03-18 Provincial Health Services Authority Dna-pk inhibiting compounds
CN112574211B (zh) * 2019-09-29 2022-06-14 山东轩竹医药科技有限公司 杂环类激酶抑制剂
CN112574179B (zh) * 2019-09-29 2022-05-10 山东轩竹医药科技有限公司 Dna-pk抑制剂
KR102786205B1 (ko) * 2019-12-31 2025-03-31 청두 바이위 파머수티컬 씨오., 엘티디 퓨린 유도체 및 의학에서의 그의 용도
CN113372345B (zh) * 2020-02-25 2022-08-16 山东轩竹医药科技有限公司 氘代杂环类激酶抑制剂
NZ793536A (en) * 2020-04-17 2025-11-28 Kangbaida Sichuan Biotechnology Co Ltd Imidazolidinone derivatives and medical use thereof
EP4263829A1 (en) 2020-12-17 2023-10-25 Vertex Pharmaceuticals Incorporated Compositions and methods for editing beta-globin for treatment of hemaglobinopathies
EP4298221A1 (en) 2021-02-26 2024-01-03 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of myotonic dystrophy type 1 with crispr/slucas9
EP4298222A1 (en) 2021-02-26 2024-01-03 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of myotonic dystrophy type 1 with crispr/sacas9
WO2023018637A1 (en) 2021-08-09 2023-02-16 Vertex Pharmaceuticals Incorporated Gene editing of regulatory elements
EP4634192A1 (en) * 2022-12-12 2025-10-22 Avelos Therapeutics Inc. Substituted heterocyclic compound derivatives and their pharmaceutical use
WO2025181336A1 (en) 2024-03-01 2025-09-04 Cellectis Sa Compositions and methods for hbb-editing in hspc
WO2025229177A1 (en) 2024-05-02 2025-11-06 Idorsia Pharmaceuticals Ltd Crystalline forms of an n-substituted indole derivative

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005026129A1 (en) * 2003-09-15 2005-03-24 Gpc Biotech Ag Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases
WO2008042639A1 (en) * 2006-10-02 2008-04-10 Irm Llc Compounds and compositions as protein kinase inhibitors
CN102137854A (zh) * 2008-06-26 2011-07-27 田边三菱制药株式会社 作为GSK3β抑制剂用于治疗神经变性疾病的4-(吡啶-4-基)-1H-(1，3，5)三嗪-2-酮衍生物

Family Cites Families (176)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571506A (en) 1989-08-14 1996-11-05 Rhone-Poulenc Rorer Pharmaceuticals Inc. Aromatic oligomeric compounds useful as mimics of bioactive macromolecules
WO1991009594A1 (en) 1989-12-28 1991-07-11 Virginia Commonwealth University Sigma receptor ligands and the use thereof
DK0498722T3 (da) 1991-02-07 1998-03-09 Roussel Uclaf Nye bicycliske nitrogenforbindelser substitueret med en benzylgruppe, fremgangsmåde til deres fremstilling, de opnåede nye intermediærer, deres anvendelse som lægemidler og de pharmaceutiske præparater som de indgår i
US6004979A (en) 1991-02-07 1999-12-21 Hoechst Marion Roussel Nitrogenous bicycles
EP0519211A1 (de) 1991-05-17 1992-12-23 Hoechst Schering AgrEvo GmbH Substituierte 4-Aminopyrimidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel
DE4208254A1 (de) 1992-03-14 1993-09-16 Hoechst Ag Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid
AU3933493A (en) 1992-04-24 1993-11-29 E.I. Du Pont De Nemours And Company Arthropodicidal and fungicidal aminopyrimidines
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
DE4437406A1 (de) 1994-10-19 1996-04-25 Hoechst Ag Chinoxaline, Verfahren zu ihrer Herstellung und ihre Verwendung
US5977117A (en) 1996-01-05 1999-11-02 Texas Biotechnology Corporation Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin
DK0968206T3 (da) 1997-02-19 2007-03-26 Berlex Inc N-heterocykliske derivater som NOS-inhibitorer
JPH10251255A (ja) 1997-03-14 1998-09-22 Nissan Chem Ind Ltd アジン誘導体
IL133009A0 (en) 1997-05-28 2001-03-19 Aventis Pharm Prod Inc Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
DE19801598C2 (de) 1998-01-17 2000-05-11 Aventis Res & Tech Gmbh & Co Katalytische Synthese von N-alkylierten Anilinen aus Olefinen und Anilinen
DE19836697A1 (de) 1998-08-13 2000-02-17 Hoechst Marion Roussel De Gmbh Substituierte 4-Amino-2-aryl-pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
WO2000042026A1 (en) 1999-01-15 2000-07-20 Novo Nordisk A/S Non-peptide glp-1 agonists
ES2306671T3 (es) * 1999-10-07 2008-11-16 Amgen Inc. Inhibidores de triazina quinasa.
GB9924092D0 (en) 1999-10-13 1999-12-15 Zeneca Ltd Pyrimidine derivatives
US6552016B1 (en) 1999-10-14 2003-04-22 Curis, Inc. Mediators of hedgehog signaling pathways, compositions and uses related thereto
AU2001234690A1 (en) 2000-02-01 2001-08-14 Cor Therapeutics, Inc. 2-(1h)-quinolone and 2-(1h)-quinoxalone inhibitors of factor xa
CA2401778C (en) 2000-02-29 2010-12-21 Cor Therapeutics, Inc. Benzamides and related inhibitors of factor xa
WO2001064646A2 (en) 2000-03-01 2001-09-07 Tularik Inc. Hydrazones and analogs as cholesterol lowering agents
DE10013318A1 (de) 2000-03-17 2001-09-20 Merck Patent Gmbh Formulierung enthaltend Chinoxalinderivate
US7498304B2 (en) 2000-06-16 2009-03-03 Curis, Inc. Angiogenesis-modulating compositions and uses
WO2002020500A2 (en) * 2000-09-01 2002-03-14 Icos Corporation Materials and methods to potentiate cancer treatment
US6613776B2 (en) 2000-09-15 2003-09-02 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
AU2001296871A1 (en) 2000-09-15 2002-03-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6610677B2 (en) 2000-09-15 2003-08-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US7473691B2 (en) 2000-09-15 2009-01-06 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6660731B2 (en) 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
ES2307667T3 (es) 2000-12-05 2008-12-01 Vertex Pharmaceuticals Incorporated Inhibidires de quinasas terminales c-jun(jnk) y otras proteinas quinasas.
HUP0400639A3 (en) 2000-12-21 2010-03-29 Vertex Pharma Pyrazole compounds useful as protein kinase inhibitors and pharmaceutical compositions containing them
US20040097502A1 (en) 2001-02-02 2004-05-20 Gellibert Francoise Jeanne Pyrazoles as tgf inhibitors
MY130778A (en) 2001-02-09 2007-07-31 Vertex Pharma Heterocyclic inhibitiors of erk2 and uses thereof
CA2441733A1 (en) 2001-03-29 2002-10-10 Vertex Pharmaceuticals Incorporated Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases
JP2004535381A (ja) 2001-04-13 2004-11-25 バーテックス　ファーマシューティカルズ　インコーポレイテッド ｃ−ＪｕｎＮ末端キナーゼ（ＪＮＫ）および他のプロテインキナーゼのインヒビター
US20030096813A1 (en) 2001-04-20 2003-05-22 Jingrong Cao Compositions useful as inhibitors of GSK-3
AU2002308748A1 (en) 2001-05-16 2002-11-25 Vertex Pharmaceuticals Incorporated Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases
MXPA03010961A (es) 2001-05-31 2004-02-27 Vertex Pharma Compuestos de tiazol utiles como inhibidores de proteinas cinasas.
JP4523271B2 (ja) 2001-06-01 2010-08-11 バーテックス ファーマシューティカルズ インコーポレイテッド プロテインキナーゼのインヒビターとして有用なチアゾール化合物
EP1399440B1 (en) 2001-06-15 2009-06-03 Vertex Pharmaceuticals Incorporated 5-(2-aminopyrimidin-4-yl)benzisoxazoles as protein kinase inhibitors
DE60214198T2 (de) 2001-07-03 2007-08-09 Vertex Pharmaceuticals Inc., Cambridge Isoxazolyl-pyrimidines als inhibitoren von src- und lck-protein-kinasen
MXPA04005510A (es) 2001-12-07 2006-02-24 Vertex Pharma Compuestos basados en pirimidina utiles como inhibidores de gsk-3.
JP4656838B2 (ja) 2002-02-06 2011-03-23 バーテックス ファーマシューティカルズ インコーポレイテッド Ｇｓｋ−３の阻害剤として有用なヘテロアリール化合物
US20030199525A1 (en) 2002-03-21 2003-10-23 Hirst Gavin C. Kinase inhibitors
US20030207873A1 (en) 2002-04-10 2003-11-06 Edmund Harrington Inhibitors of Src and other protein kinases
WO2003091246A1 (en) 2002-04-26 2003-11-06 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
CA2485429A1 (en) 2002-05-06 2004-07-15 Vertex Pharmaceuticals Incorporated Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase
KR20050013562A (ko) 2002-05-30 2005-02-04 버텍스 파마슈티칼스 인코포레이티드 Ｊａｋ 및 ｃｄｋ2 프로테인 키나아제의 억제제
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
US20040208608A1 (en) 2002-06-24 2004-10-21 Alex Tager Dispersion compensation architecture for switch-ready optical networks
CA2491895C (en) 2002-07-09 2011-01-18 Vertex Pharmaceuticals Incorporated Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases
RU2005106871A (ru) 2002-08-14 2005-10-10 Вертекс Фармасьютикалз Инкорпорейтед (Us) Ингибиторы протеинкиназ и их применение
US7419984B2 (en) 2002-10-17 2008-09-02 Cell Therapeutics, Inc. Pyrimidines and uses thereof
EP2172460A1 (en) 2002-11-01 2010-04-07 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of JAK and other protein kinases
US7259161B2 (en) 2002-11-04 2007-08-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of JAK and other protein kinases
US7226919B2 (en) 2002-12-18 2007-06-05 Vertex Pharmaceuticals Inc. Compositions useful as inhibitors of protein kinases
US7144911B2 (en) 2002-12-31 2006-12-05 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
US7452555B2 (en) 2003-01-21 2008-11-18 S.S.C.I., Inc. Cocrystallization
US7407962B2 (en) 2003-02-07 2008-08-05 Vertex Pharmaceuticals Incorporated Heteroaryl compounds useful as inhibitors or protein kinases
US7456190B2 (en) 2003-03-13 2008-11-25 Vertex Pharmaceuticals Incorporated Compositions useful as protein kinase inhibitors
US8404681B2 (en) 2003-03-24 2013-03-26 Luitpold Pharmaceuticals, Inc. Xanthones, thioxanthones and acridinones as DNA-PK inhibitors
WO2004087698A2 (en) 2003-03-25 2004-10-14 Vertex Pharmaceuticals Incorporated Thiazoles useful as inhibitors of protein kinases
US6875781B2 (en) 2003-04-04 2005-04-05 Cell Therapeutics, Inc. Pyridines and uses thereof
US7189724B2 (en) 2003-04-15 2007-03-13 Valeant Research And Development Quinoxaline derivatives having antiviral activity
CA2547080A1 (en) 2003-12-02 2005-07-28 Vertex Pharmaceuticals, Inc. Heterocyclic protein kinase inhibitors and uses thereof
CA2548172A1 (en) 2003-12-04 2005-06-23 Vertex Pharmaceuticals Incorporated Quinoxalines useful as inhibitors of protein kinases
TW200533357A (en) 2004-01-08 2005-10-16 Millennium Pharm Inc 2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases
AU2005222622B2 (en) 2004-03-15 2011-04-07 Dainippon Sumitomo Pharma Co., Ltd. SNS-595 and methods of using the same
GB0405985D0 (en) 2004-03-17 2004-04-21 Novartis Forschungsstiftung Kinase
MXPA06013208A (es) 2004-05-14 2007-01-16 Vertex Pharma Profarmacos de pirrolipirimidina como inhibidotes de la proteina cinasa erk.
JP4449580B2 (ja) 2004-05-31 2010-04-14 宇部興産株式会社 ４−アラルキルアミノピリミジン誘導体及び抗菌剤
UA92150C2 (ru) 2004-06-04 2010-10-11 Арена Фармасьютикалз, Инк. Замещенные производные арила и гетероарила как модуляторы метаболизма и для профилактики и лечения связанных с ним расстройств
ATE493401T1 (de) 2004-09-17 2011-01-15 Vertex Pharma Als proteinkinaseinhibitoren geeignete diaminotriazolverbindungen
EP2402323A3 (en) 2004-10-13 2012-05-30 PTC Therapeutics, Inc. Pyrazole or triazole compounds and their use for the manufacture of a medicament for treating somatic mutation-related diseases
HN2005000795A (es) 2004-10-15 2010-08-19 Aventis Pharma Inc Pirimidinas como antagonistas del receptor de prostaglandina d2
JP2008516939A (ja) 2004-10-15 2008-05-22 アストラゼネカ アクチボラグ 化学化合物
US20060166936A1 (en) 2004-10-29 2006-07-27 Hayley Binch Diaminotriazole compounds useful as inhibitors of protein kinases
US7517870B2 (en) 2004-12-03 2009-04-14 Fondazione Telethon Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization
AU2005316599A1 (en) 2004-12-14 2006-06-22 Vertex Pharmaceuticals Incorporated Pyrimidine inhibitors of ERK protein kinase and uses therof
US7501415B2 (en) 2004-12-23 2009-03-10 Vertex Pharmaceuticals Incorporated Selective inhibitors of ERK protein kinase and uses thereof
MY158077A (en) 2005-02-04 2016-08-30 Senomyx Inc Compounds comprising linked heteroaryl moieties and their use as novel umami flavor modifiers tastants and taste enhancers for comestible compositions
CN101184395A (zh) 2005-04-06 2008-05-21 Irm责任有限公司 包含二芳基胺的化合物和组合物及其作为类固醇激素核受体调节剂的用途
AR053358A1 (es) 2005-04-15 2007-05-02 Cancer Rec Tech Ltd Inhibidores de adn - pk
EP1901747A2 (en) * 2005-05-25 2008-03-26 Ingenium Pharmaceuticals AG Pyrimidine-based cdk inhibitors for treating pain
WO2006138418A2 (en) 2005-06-14 2006-12-28 President And Fellows Of Harvard College Improvement of cognitive performance with sirtuin activators
JP2007008045A (ja) 2005-06-30 2007-01-18 Mitsui Chemicals Inc 光記録媒体および１ｈ−キノキサリン−２−オン誘導体
US7874452B2 (en) 2005-07-22 2011-01-25 Berkeley Law & Technology Group, Llp Cup cover
AU2006272609A1 (en) 2005-07-26 2007-02-01 Vertex Pharmaceuticals Incorporated Abl kinase inhibition
GB0520657D0 (en) 2005-10-11 2005-11-16 Ludwig Inst Cancer Res Pharmaceutical compounds
US20070219192A1 (en) 2005-11-02 2007-09-20 Xiangping Qian Certain chemical entities, compositions, and methods
CN101316597B (zh) 2005-11-03 2013-04-17 顶点医药品公司 用作激酶抑制剂的氨基嘧啶
DE602006021776D1 (de) 2005-11-16 2011-06-16 Vertex Pharma Als kinaseinhibitoren geeignete aminopyrimidine
EP1983823A1 (en) 2006-01-17 2008-10-29 VIB vzw Inhibitors of prolyl-hydroxylase 1 for the treatment of skeletal muscle degeneration
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
PE20071025A1 (es) 2006-01-31 2007-10-17 Mitsubishi Tanabe Pharma Corp Compuesto amina trisustituido
WO2007109783A2 (en) 2006-03-23 2007-09-27 Janssen Pharmaceutica, N.V. Substituted pyrimidine kinase inhibitors
US20080280891A1 (en) 2006-06-27 2008-11-13 Locus Pharmaceuticals, Inc. Anti-cancer agents and uses thereof
WO2008008852A2 (en) 2006-07-11 2008-01-17 Emory University Cxcr4 antagonists including heteroatoms for the treatment of medical disorders
TW200811134A (en) 2006-07-12 2008-03-01 Irm Llc Compounds and compositions as protein kinase inhibitors
AR061974A1 (es) 2006-07-14 2008-08-10 Novartis Ag Derivados de pirimidina como inhibidores de alk, composiciones farmaceuticas y procesos de obtencion
PE20121506A1 (es) * 2006-07-14 2012-11-26 Amgen Inc Compuestos triazolopiridinas como inhibidores de c-met
US7635683B2 (en) 2006-08-04 2009-12-22 Enanta Pharmaceuticals, Inc. Quinoxalinyl tripeptide hepatitis C virus inhibitors
EP2589597B1 (en) 2006-08-22 2019-03-06 Technion Research & Development Foundation Heterocyclic derivatives binding to the peripheral-type benzodiazepine receptor (PBR)
EP1903038A1 (de) 2006-09-07 2008-03-26 Bayer Schering Pharma Aktiengesellschaft N-(1-Hetaryl-piperidin-4-yl)-(het)arylamide als EP2-Rezeptor Modulatoren
US7875603B2 (en) 2006-09-21 2011-01-25 Nova Southeastern University Specific inhibitors for vascular endothelial growth factor receptors
DE102006050512A1 (de) 2006-10-26 2008-04-30 Bayer Healthcare Ag Substituierte heterocyclische Verbindungen und ihre Verwendung
EP2086965B1 (en) 2006-11-02 2010-02-10 Vertex Pharmaceuticals, Inc. Aminopyridines and aminopyrimidines useful as inhibitors of protein kinases
JP2010511727A (ja) 2006-12-04 2010-04-15 ニューロクライン バイオサイエンシーズ，インコーポレイテッド アデノシン受容体アンタゴニストとしての置換ピリミジン
AU2007333650A1 (en) 2006-12-19 2008-06-26 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as inhibitors of protein kinases
KR20090102838A (ko) 2006-12-28 2009-09-30 암브룩스, 인코포레이티드 페나진 및 퀴녹살린 치환된 아미노산 및 폴리펩티드
AU2008210266B2 (en) 2007-01-31 2013-09-05 Ym Biosciences Australia Pty Ltd Thiopyrimidine-based compounds and uses thereof
WO2008106202A1 (en) 2007-02-27 2008-09-04 Housey Gerard M Theramutein modulators
MX2009009590A (es) 2007-03-09 2009-11-10 Vertex Pharma Aminopirimidinas utiles como inhibidores de proteinas cinasas.
JP2010520887A (ja) 2007-03-09 2010-06-17 バーテックス ファーマシューティカルズ インコーポレイテッド 蛋白キナーゼの阻害剤として有用なアミノピリジン
JP5393489B2 (ja) 2007-03-09 2014-01-22 バーテックス ファーマシューティカルズ インコーポレイテッド 蛋白キナーゼの阻害剤として有用なアミノピリミジン
MX2009010037A (es) 2007-03-20 2009-11-05 Vertex Pharma Aminopirimidinas utiles como inhibidores de cinasas.
DE102007015169A1 (de) 2007-03-27 2008-10-02 Universität des Saarlandes Campus Saarbrücken 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen
CA2683785A1 (en) 2007-04-13 2008-10-23 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as kinase inhibitors
US7910587B2 (en) 2007-04-26 2011-03-22 Enanta Pharmaceuticals, Inc. Quinoxalinyl dipeptide hepatitis C virus inhibitors
MX2009011811A (es) 2007-05-02 2010-01-14 Vertex Pharma Aminopirimidinas utiles como inhibidores de cinasa.
CA2694381A1 (en) 2007-05-02 2008-11-13 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as kinase inhibitors
JP5389785B2 (ja) 2007-05-02 2014-01-15 バーテックス ファーマシューティカルズ インコーポレイテッド キナーゼ阻害剤として有用なチアゾールおよびピラゾール
JP2010526823A (ja) 2007-05-10 2010-08-05 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー Ｐｉ３キナーゼ阻害物質としてのキノキサリン誘導体
WO2008144253A1 (en) 2007-05-14 2008-11-27 Irm Llc Protein kinase inhibitors and methods for using thereof
CN101687852A (zh) 2007-05-24 2010-03-31 沃泰克斯药物股份有限公司 可用作激酶抑制剂的噻唑类和吡唑类化合物
WO2008145616A1 (en) 2007-05-25 2008-12-04 Abbott Gmbh & Co. Kg Heterocyclic compounds as positive modulators of metabotropic glutamate receptor 2 (mglu2 receptor)
WO2009004621A1 (en) 2007-07-02 2009-01-08 Technion Research & Development Foundation Ltd. Compositions, articles and methods comprising tspo ligands for preventing or reducing tobacco-associated damage
EP2170338A2 (en) 2007-07-06 2010-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Dna-pkcs modulates energy regulation and brain function
UY31232A1 (es) 2007-07-19 2009-03-02 Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones
EP2174934B1 (en) 2007-08-01 2012-06-06 Kumiai Chemical Industry Co., Ltd. Oxopyrazine derivative and herbicide
EP2190466A4 (en) 2007-08-10 2011-12-21 Burnham Inst Medical Research Tissue-specific alkaline phosphatase (TNAP) activators and their use
DE102007044032A1 (de) 2007-09-14 2009-03-19 Bayer Healthcare Ag Substituierte heterocyclische Verbindungen und ihre Verwendung
NZ584454A (en) 2007-10-12 2011-09-30 Ingenium Pharmaceuticals Gmbh N-[6-phenyl-pyrimidin-4-yl]-amides and urea derivatives as inhibitors of protein kinases
CN101902912A (zh) 2007-11-06 2010-12-01 纳幕尔杜邦公司 杀真菌杂环胺
US20120009151A1 (en) 2007-12-21 2012-01-12 Progenics Pharmaceuticals, Inc. Triazines And Related Compounds Having Antiviral Activity, Compositions And Methods Thereof
CA2714743C (en) 2008-02-19 2017-01-17 Janssen Pharmaceutica N.V. Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase
US20110009421A1 (en) 2008-02-27 2011-01-13 Takeda Pharmaceutical Company Limited Compound having 6-membered aromatic ring
CN101952258B (zh) 2008-03-05 2014-03-19 默克专利有限公司 作为胰岛素分泌刺激剂的喹喔啉酮衍生物、获得它们的方法及其在治疗糖尿病中的用途
US8268834B2 (en) 2008-03-19 2012-09-18 Novartis Ag Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme
CA2725316A1 (en) 2008-06-02 2009-12-10 Banyu Pharmaceutical Co., Ltd. Novel isoxazole derivative
MX2010013577A (es) 2008-06-16 2010-12-21 Merck Patent Gmbh Derivados de quinoxalindiona.
WO2010011756A1 (en) 2008-07-23 2010-01-28 Vertex Pharmaceuticals Incorporated Pyrazolopyridine kinase inhibitors
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
EP2362775B1 (en) 2008-11-20 2015-08-05 GlaxoSmithKline LLC Chemical compounds
WO2010065899A2 (en) 2008-12-05 2010-06-10 Molecular Insight Pharmaceuticals, Inc. Technetium-and rhenium-bis(heteroaryl)complexes and methods of use thereof
AU2009327357C1 (en) 2008-12-19 2017-02-02 Vertex Pharmaceuticals Incorporated Pyrazine derivatives useful as inhibitors of ATR kinase
CA2752150A1 (en) 2009-02-11 2010-08-19 Reaction Biology Corp. Selective kinase inhibitors
JP2010111702A (ja) 2009-02-16 2010-05-20 Tetsuya Nishio 複素環化合物、その製造法および用途
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
WO2011022348A1 (en) 2009-08-18 2011-02-24 Janssen Pharmaceutica Nv Ethylene diamine modulators of fatty acid amide hydrolase
AR077999A1 (es) 2009-09-02 2011-10-05 Vifor Int Ag Antagonistas de pirimidin y triazin-hepcidina
IN2012DN03312A (OSRAM) 2009-10-22 2015-10-23 Fibrotech Therapeutics Pty Ltd
ES2360333B1 (es) 2009-10-29 2012-05-04 Consejo Superior De Investigaciones Cientificas (Csic) (70%) Derivados de bis (aralquil) amino y sistemas (hetero) aromaticos de seis miembros y su uso en el tratamiento de patologias neurodegenerativas, incluida la enfermedad de alzheimer
EP2495238A4 (en) 2009-10-30 2013-04-24 Mochida Pharm Co Ltd NEW 3-HYDROXY-5-ARYLISOXAZOLE DERIVATIVE
MX2012007474A (es) 2009-12-25 2012-08-01 Mochida Pharm Co Ltd Derivados de 3-hidroxi-5-arilisotiazol novedosos.
UY33213A (es) 2010-02-18 2011-09-30 Almirall Sa Derivados de pirazol como inhibidores de jak
EA201201289A1 (ru) 2010-03-16 2013-08-30 Мерк Патент Гмбх Морфолинилхиназолины
TWI516264B (zh) 2010-05-06 2016-01-11 臺北醫學大學 芳香醯喹啉化合物
JP2011246389A (ja) 2010-05-26 2011-12-08 Oncotherapy Science Ltd Ｔｔｋ阻害作用を有する縮環ピラゾール誘導体
DE102010025786A1 (de) 2010-07-01 2012-01-05 Merck Patent Gmbh Pyrazolochinoline
DE102010035744A1 (de) 2010-08-28 2012-03-01 Merck Patent Gmbh Imidazolonylchinoline
US9464065B2 (en) 2011-03-24 2016-10-11 The Scripps Research Institute Compounds and methods for inducing chondrogenesis
MX2013011450A (es) 2011-04-05 2014-02-03 Vertex Pharma Compuestos de aminopirazina utiles como inhibidores de la cinasa ataxia telangiectasia mutada y rad3 relacionados (atr).
GB201114051D0 (en) 2011-08-15 2011-09-28 Domainex Ltd Compounds and their uses
ES2725790T3 (es) 2011-08-26 2019-09-27 Neupharma Inc Algunas entidades químicas, composiciones, y métodos
WO2013040515A1 (en) 2011-09-14 2013-03-21 Neupharma, Inc. Certain chemical entities, compositions, and methods
WO2013043935A1 (en) 2011-09-21 2013-03-28 Neupharma, Inc. Certain chemical entites, compositions, and methods
US9249111B2 (en) 2011-09-30 2016-02-02 Neupharma, Inc. Substituted quinoxalines as B-RAF kinase inhibitors
DE102011118830A1 (de) 2011-11-18 2013-05-23 Merck Patent Gmbh Morpholinylbenzotriazine
GB201120993D0 (en) 2011-12-06 2012-01-18 Imp Innovations Ltd Novel compounds and their use in therapy
WO2013112950A2 (en) 2012-01-25 2013-08-01 Neupharma, Inc. Certain chemical entities, compositions, and methods
EP2841428B1 (en) * 2012-04-24 2018-08-22 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
EP2916838B1 (en) 2012-11-12 2019-03-13 Neupharma, Inc. Certain chemical entities, compositions, and methods
WO2014159690A1 (en) 2013-03-12 2014-10-02 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
PL3424920T3 (pl) 2013-10-17 2020-11-16 Vertex Pharmaceuticals Incorporated Kokryształy (S)-N-metylo-8-(1-((2'-metylo-4’,6'-dideutero-[4,5'-bipirymidyn]-6-ylo)amino)propan-2-ylo)chinolino-4-karboksyamidu i ich deuterowane pochodne jako inhibitory DNA-PK

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005026129A1 (en) * 2003-09-15 2005-03-24 Gpc Biotech Ag Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases
WO2008042639A1 (en) * 2006-10-02 2008-04-10 Irm Llc Compounds and compositions as protein kinase inhibitors
CN102137854A (zh) * 2008-06-26 2011-07-27 田边三菱制药株式会社 作为GSK3β抑制剂用于治疗神经变性疾病的4-(吡啶-4-基)-1H-(1，3，5)三嗪-2-酮衍生物

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