EA029568B8 - Бигетероарильные соединения и их применения - Google Patents

Бигетероарильные соединения и их применения

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Publication number
EA029568B8
EA029568B8 EA201592060A EA201592060A EA029568B8 EA 029568 B8 EA029568 B8 EA 029568B8 EA 201592060 A EA201592060 A EA 201592060A EA 201592060 A EA201592060 A EA 201592060A EA 029568 B8 EA029568 B8 EA 029568B8
Authority
EA
Eurasian Patent Office
Prior art keywords
compounds
biheteroaryl compounds
biheteroaryl
formula
diseases
Prior art date
Application number
EA201592060A
Other languages
English (en)
Other versions
EA201592060A1 (ru
EA029568B1 (ru
Inventor
Кевин С. Чэнь
Литин Дун
Энтони Эстрада
Пол Гиббонс
Малкольм Хуэстис
Терри Келлар
Вэнь Лю
Джозеф П. Лиссикатос
Чаню Ма
Алан Оливеро
Снахель Патель
Даниэль Шор
Майкл Сиу
Original Assignee
Ф.Хоффманн-Ля Рош Аг
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ф.Хоффманн-Ля Рош Аг filed Critical Ф.Хоффманн-Ля Рош Аг
Publication of EA201592060A1 publication Critical patent/EA201592060A1/ru
Publication of EA029568B1 publication Critical patent/EA029568B1/ru
Publication of EA029568B8 publication Critical patent/EA029568B8/ru

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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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  • AIDS & HIV (AREA)
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Abstract

В изобретении предложены соединения формулы I-I, их воплощения и соли для лечения заболеваний (например, нейродегенеративных заболеваний). Все переменные R, R, R, X, X, A и Cy в формуле I-I имеют значение, определенное в данном документе.
EA201592060A 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения EA029568B8 (ru)

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Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX363118B (es) * 2012-05-03 2019-03-11 Genentech Inc Derivados de pirazol aminopirimidina como moduladores de cinasa 2 de repeticion rica en leucina (lrrk2).
RU2015131314A (ru) * 2013-01-18 2017-02-27 Ф. Хоффманн-Ля Рош Аг 3-замещенные пиразолы и их применение в качестве ингибиторов dlk
KR20160002850A (ko) * 2013-05-01 2016-01-08 에프. 호프만-라 로슈 아게 C-연결된 헤테로사이클로알킬 치환된 피리미딘 및 이의 용도
PE20161063A1 (es) 2013-05-01 2016-10-22 Hoffmann La Roche Compuestos de biheteroarilo y usos de los mismos
MX2016008110A (es) * 2013-12-20 2016-08-19 Hoffmann La Roche Derivados de pirazol como inhibidores de la cinasa de cremallera de leucina dual (dlk) y usos de los mismos.
CN104926716A (zh) * 2015-06-10 2015-09-23 哈尔滨工业大学 吡啶衍生物2,6-二[(6-甲氧基吡啶-2-基)甲基]吡啶及其合成方法
EA201990450A1 (ru) * 2016-08-29 2019-07-31 Боард Оф Реджентс, Де Юниверсити Оф Техас Систем Ингибиторы киназы, содержащей домен с двумя лейциновыми "застежками-молниями" (dlk), для лечения заболевания
EP3551610B1 (en) 2016-12-08 2021-08-11 Board of Regents, The University of Texas System Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease
EP3652178B1 (en) 2017-07-14 2024-01-24 F. Hoffmann-La Roche AG Bicyclic ketone compounds and methods of use thereof
JP7362600B2 (ja) 2017-10-11 2023-10-17 エフ． ホフマン－ラ ロシュ アーゲー Ｒｉｐ１キナーゼ阻害剤として使用するための二環式化合物
CN111465602B (zh) * 2017-10-17 2023-05-23 帕劳制药有限公司 4-氨基嘧啶化合物的合成
RU2020115915A (ru) 2017-10-31 2021-12-01 Ф. Хоффманн-Ля Рош Аг Бициклические сульфоны и сульфоксиды и способы их применения
CN112074519B (zh) 2018-04-20 2024-08-02 豪夫迈·罗氏有限公司 作为rip1激酶抑制剂用于治疗例如肠易激综合征(ibs)的化合物
CA3116339A1 (en) 2018-10-22 2020-04-30 Cadent Therapeutics, Inc. Crystalline forms of potassium channel modulators
CA3123215C (en) 2018-12-19 2024-04-02 Disarm Therapeutics, Inc. Inhibitors of sarm1 in combination with neuroprotective agents
JP2022516651A (ja) 2019-01-11 2022-03-01 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 二環式ピロロトリアゾールケトン化合物及びその使用方法
AU2020214889A1 (en) * 2019-01-31 2021-09-02 The National Institutes of Pharmaceutical R&D Co., Ltd. Aromatic ring or heteroaromatic ring compounds, preparation method therefor and medical use thereof
US11560366B2 (en) 2019-10-21 2023-01-24 Board Of Regents, The University Of Texas System Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (DLK) kinase for the treatment of disease
MX2023003759A (es) * 2020-10-02 2023-04-24 Genentech Inc Proceso para la preparacion de compuestos de biheteroarilo y formas cristalinas de estos.
EP4395899A1 (en) * 2021-09-01 2024-07-10 The United States of America, as represented by the Secretary, Department of Health and Human Services Mixed lineage kinase inhibitors and methods of use
EP4419105A1 (en) * 2021-10-20 2024-08-28 Yousef Najajreh Allosteric inhibitor compounds for overcoming cancer resistance
WO2024156938A1 (en) 2023-01-28 2024-08-02 Orion Corporation Cbl-b inhibitors

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
EP0102324A3 (de) 1982-07-29 1984-11-07 Ciba-Geigy Ag Lipide und Tenside in wässriger Phase
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
US5004697A (en) 1987-08-17 1991-04-02 Univ. Of Ca Cationized antibodies for delivery through the blood-brain barrier
US5112596A (en) 1990-04-23 1992-05-12 Alkermes, Inc. Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability
US5268164A (en) 1990-04-23 1993-12-07 Alkermes, Inc. Increasing blood-brain barrier permeability with permeabilizer peptides
EP0652775B1 (en) 1992-07-27 2000-04-19 THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES Targeting of liposomes to the blood-brain barrier
US6514221B2 (en) 2000-07-27 2003-02-04 Brigham And Women's Hospital, Inc. Blood-brain barrier opening
AU2001286930A1 (en) 2000-08-30 2002-03-13 The Board Of Trustees Of The Leland Stanford Junior University Glucocorticoid blocking agents for increasing blood-brain barrier permeability
US7034036B2 (en) 2000-10-30 2006-04-25 Pain Therapeutics, Inc. Inhibitors of ABC drug transporters at the blood-brain barrier
DE10121982B4 (de) 2001-05-05 2008-01-24 Lts Lohmann Therapie-Systeme Ag Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung
DE60234057D1 (de) 2001-07-25 2009-11-26 Raptor Pharmaceutical Inc Zusammensetzungen und verfahren zur modulation des transports durch die blut-hirn-schranke
US20030162695A1 (en) 2002-02-27 2003-08-28 Schatzberg Alan F. Glucocorticoid blocking agents for increasing blood-brain barrier permeability
SI1549652T1 (sl) 2002-09-30 2009-04-30 Bayer Healthcare Ag Kondenzirani azolpirimidinski derivati
JP4995423B2 (ja) 2002-12-03 2012-08-08 ブランシェット・ロックフェラー・ニューロサイエンスィズ・インスティテュート 物質を血液−脳関門を渡って輸送するための人工低密度リポタンパク質キャリア
WO2005025511A2 (en) 2003-09-10 2005-03-24 Cedars-Sinai Medical Center Potassium channel mediated delivery of agents through the blood-brain barrier
GB0508471D0 (en) 2005-04-26 2005-06-01 Celltech R&D Ltd Therapeutic agents
JO2660B1 (en) * 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
WO2008064244A2 (en) 2006-11-20 2008-05-29 The Trustees Of Columbia University In The City Of New York Phosphoinositide modulation for the treatment of neurodegenerative diseases
JP2010518107A (ja) * 2007-02-06 2010-05-27 ノバルティス アーゲー Ｐｉ３−キナーゼ阻害剤およびその使用方法
BRPI0814441A2 (pt) 2007-07-19 2015-07-14 Schering Corp Compostos de amida heterocíclica como inibidores de proteína cinase
WO2009066084A1 (en) * 2007-11-21 2009-05-28 F. Hoffmann-La Roche Ag 2 -morpholinopyrimidines and their use as pi3 kinase inhibitors
US20100056609A1 (en) 2008-08-26 2010-03-04 Washington University Methods and compositions for inhibition of axonal degeneration by modulation of the dlk/jnk pathway
RU2538683C2 (ru) * 2008-10-31 2015-01-10 Новартис Аг КОМБИНАЦИЯ ИНГИБИТОРА ФОСФАТИДИЛИНОЗИТОЛ-3-КИНАЗЫ (Р13К) И ИНГИБИТОРА mTOR
GB2465405A (en) * 2008-11-10 2010-05-19 Univ Basel Triazine, pyrimidine and pyridine analogues and their use in therapy
NZ598808A (en) 2009-09-09 2014-07-25 Celgene Avilomics Res Inc Pi3 kinase inhibitors and uses thereof
CN104043126A (zh) 2009-10-22 2014-09-17 霍夫曼-拉罗奇有限公司 轴突变性的调节
GB201004200D0 (en) 2010-03-15 2010-04-28 Univ Basel Spirocyclic compounds and their use as therapeutic agents and diagnostic probes
NZ603644A (en) 2010-05-24 2014-10-31 Univ Rochester Bicyclic heteroaryl kinase inhibitors and methods of use
CA2829558A1 (en) * 2011-03-09 2012-09-13 Celgene Avilomics Research, Inc. Pi3 kinase inhibitors and uses thereof
PE20161063A1 (es) * 2013-05-01 2016-10-22 Hoffmann La Roche Compuestos de biheteroarilo y usos de los mismos
CN103483345B (zh) 2013-09-25 2016-07-06 中山大学 Pi3k激酶抑制剂、包含其的药物组合物及其应用
JP5920747B1 (ja) 2015-04-07 2016-05-18 エイピーエス．エスエイ アプリケーションプログラムおよびカード

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