TW201716415A - 作為蛋白質激酶之調節劑的掌性二芳基巨環 - Google Patents

作為蛋白質激酶之調節劑的掌性二芳基巨環 Download PDF

Info

Publication number
TW201716415A
TW201716415A TW105121035A TW105121035A TW201716415A TW 201716415 A TW201716415 A TW 201716415A TW 105121035 A TW105121035 A TW 105121035A TW 105121035 A TW105121035 A TW 105121035A TW 201716415 A TW201716415 A TW 201716415A
Authority
TW
Taiwan
Prior art keywords
alkyl
nhs
nhc
group
cycloalkyl
Prior art date
Application number
TW105121035A
Other languages
English (en)
Chinese (zh)
Inventor
景榮 崔
一山 李
埃文W 羅杰斯
大勇 翟
維 鄧
珍 翁
Original Assignee
Tp生物醫藥公司
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 Tp生物醫藥公司 filed Critical Tp生物醫藥公司
Publication of TW201716415A publication Critical patent/TW201716415A/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
TW105121035A 2015-07-02 2016-07-01 作為蛋白質激酶之調節劑的掌性二芳基巨環 TW201716415A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562188043P 2015-07-02 2015-07-02
US201662353728P 2016-06-23 2016-06-23

Publications (1)

Publication Number Publication Date
TW201716415A true TW201716415A (zh) 2017-05-16

Family

ID=57609146

Family Applications (1)

Application Number Title Priority Date Filing Date
TW105121035A TW201716415A (zh) 2015-07-02 2016-07-01 作為蛋白質激酶之調節劑的掌性二芳基巨環

Country Status (13)

Country Link
US (2) US10316044B2 (enExample)
EP (1) EP3317285B1 (enExample)
JP (1) JP6871903B2 (enExample)
KR (1) KR102599788B1 (enExample)
CN (1) CN107735399B (enExample)
AU (2) AU2016287568B2 (enExample)
CA (1) CA2989327A1 (enExample)
ES (1) ES2864839T3 (enExample)
IL (1) IL256377A (enExample)
MX (1) MX2017017097A (enExample)
RU (1) RU2732405C2 (enExample)
TW (1) TW201716415A (enExample)
WO (1) WO2017004342A1 (enExample)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2350075T1 (sl) 2008-09-22 2014-06-30 Array Biopharma, Inc. Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji
CN102264736B (zh) 2008-10-22 2013-08-14 阵列生物制药公司 作为TRK激酶抑制剂的取代的吡唑并[1,5-a]嘧啶化合物
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
BR122019024201B1 (pt) 2010-05-20 2021-08-03 Array Biopharma Inc Composto macrocíclico como inibidores de trk quinase, seu uso, e composição farmacêutica
WO2015112806A2 (en) 2014-01-24 2015-07-30 Tp Therapeutics, Inc. Diaryl macrocycles as modulators of protein kinases
TWI746426B (zh) 2014-11-16 2021-11-21 美商亞雷生物製藥股份有限公司 (S)-N-(5-((R)-2-(2,5-二氟苯基)-吡咯啶-1-基)-吡唑并[1,5-a]嘧啶-3-基)-3-羥基吡咯啶-1-甲醯胺硫酸氫鹽結晶型
RU2732405C2 (ru) 2015-07-02 2020-09-16 Тёрнинг Поинт Терапьютикс, Инк. Хиральные диарильные макроциклы в качестве модуляторов протеинкиназ
BR112018000297A2 (pt) 2015-07-06 2018-09-04 Tp Therapeutics Inc polimorfo de macrociclo de diarila
WO2017015367A1 (en) * 2015-07-21 2017-01-26 Tp Therapeutics, Inc. Chiral diaryl macrocycles and uses thereof
EP3368039A1 (en) 2015-10-26 2018-09-05 The Regents of The University of Colorado, A Body Corporate Point mutations in trk inhibitor-resistant cancer and methods relating to the same
UA125025C2 (uk) 2016-04-04 2021-12-29 Локсо Онколоджі, Інк. Способи лікування дитячих ракових захворювань
UA125026C2 (uk) 2016-04-04 2021-12-29 Локсо Онколоджі, Інк. РІДКІ КОМПОЗИЦІЇ (S)-N-(5-((R)-2-(2,5-ДИФТОРФЕНІЛ)ПІРОЛІДИН-1-ІЛ)ПІРАЗОЛО[1,5-a]ПІРИМІДИН-3-ІЛ)-3-ГІДРОКСИПІРОЛІДИН-1-КАРБОКСАМІДУ
MX392604B (es) 2016-05-18 2025-03-24 Array Biopharma Inc Procesos para la preparacion de (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida y sales del mismo.
AU2017292646A1 (en) * 2016-07-05 2019-02-07 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
AU2017302019A1 (en) * 2016-07-28 2019-02-07 Turning Point Therapeutics, Inc. Macrocycle kinase inhibitors
US10934261B2 (en) 2016-09-28 2021-03-02 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
TWI808958B (zh) * 2017-01-25 2023-07-21 美商特普醫葯公司 涉及二芳基巨環化合物之組合療法
JOP20190213A1 (ar) * 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
CN107586796B (zh) * 2017-07-20 2021-08-06 暨明医药科技(苏州)有限公司 (r)-2-(1-氨基乙基)-4-氟苯酚的合成方法
PT3658148T (pt) 2017-07-28 2024-08-26 Turning Point Therapeutics Inc Compostos macrocíclicos e utilizações dos mesmos
KR102619444B1 (ko) 2017-08-23 2023-12-29 치아타이 티안큉 파마수티컬 그룹 주식회사 아미노피라졸 및 피리미딘을 함유하는 마크로사이클 및 그의 약학적 조성물 및 용도
CN109516999B (zh) * 2017-11-01 2021-08-17 郑州泰基鸿诺医药股份有限公司 用作蛋白质激酶调节剂的化合物及其应用
CA3081790C (en) * 2017-11-10 2023-03-07 Angex Pharmaceutical, Inc. Macrocyclic compounds as trk kinase inhibitors and uses thereof
RS63787B1 (sr) 2017-12-19 2022-12-30 Turning Point Therapeutics Inc Makrociklična jedinjenja za lečenje bolesti
CN109456331B (zh) 2017-12-22 2020-06-05 深圳市塔吉瑞生物医药有限公司 一种取代的吡唑并[1,5-a]嘧啶化合物及其药物组合物及用途
WO2019144885A1 (zh) * 2018-01-23 2019-08-01 深圳市塔吉瑞生物医药有限公司 取代的吡唑并[1,5-a]嘧啶类的大环化合物
WO2019149131A1 (zh) * 2018-01-30 2019-08-08 上海吉倍生物技术有限公司 具有大环分子结构的化合物及其用途
JP2021519297A (ja) * 2018-03-28 2021-08-10 フォチョン・ファーマシューティカルズ・リミテッドFochon Pharmaceuticals, Ltd. Trkキナーゼ阻害剤としての大環状化合物
US11584759B2 (en) 2018-04-18 2023-02-21 Hitgen Inc. Macrocyclic kinase inhibitor
CN111918868B (zh) * 2018-05-04 2022-12-30 正大天晴药业集团股份有限公司 作为蛋白激酶调节剂的二芳基大环化合物
CN110577532B (zh) * 2018-06-08 2022-06-03 江苏威凯尔医药科技有限公司 原肌球蛋白受体激酶抑制剂及其制备方法和应用
WO2019233461A1 (zh) * 2018-06-08 2019-12-12 江苏威凯尔医药科技有限公司 原肌球蛋白受体激酶抑制剂及其制备方法和应用
CN110950889B (zh) * 2018-09-27 2022-04-05 北京赛林泰医药技术有限公司 一种多靶点激酶抑制剂及其制备方法和用途
EP3858834A4 (en) * 2018-09-29 2022-06-22 Shandong Luye Pharmaceutical Co., Ltd. PYRAZOLOPYRIMIDE DERIVATIVES AS SELECTIVE TRK INHIBITORS
RS66346B1 (sr) 2018-10-22 2025-01-31 Alumis Inc Inhibitori tyk2 i njihova upotreba
CN111171049B (zh) * 2018-11-09 2021-06-04 山东轩竹医药科技有限公司 酪氨酸激酶抑制剂及其用途
CN111171019A (zh) 2018-11-13 2020-05-19 上海轶诺药业有限公司 一类五元并六元杂环化合物及其作为蛋白受体激酶抑制剂的用途
CN111171020A (zh) 2018-11-13 2020-05-19 上海轶诺药业有限公司 一类六元并六元杂环化合物及其作为蛋白受体激酶抑制剂的用途
US20220177486A1 (en) * 2019-03-11 2022-06-09 Esker Therapeutics, Inc. Tyk2 inhibitors and uses thereof
SG11202110523XA (en) * 2019-03-26 2021-10-28 Ventyx Biosciences Inc Tyk2 pseudokinase ligands
US12410191B2 (en) 2019-05-21 2025-09-09 Zhejiang Hisun Pharmaceutical Co., Ltd. Macrolide derivatives, preparation method and application thereof
WO2020257189A1 (en) * 2019-06-19 2020-12-24 Turning Point Therapeutics, Inc. Macrocycles for treating disease
WO2020257165A1 (en) * 2019-06-19 2020-12-24 Turning Point Therapeutics, Inc. Macrocycles for use in treating disease
WO2020257169A1 (en) * 2019-06-19 2020-12-24 Turning Point Therapeutics, Inc. Polymorphs of a macrocyclic kinase inhibitor
WO2021027503A1 (zh) * 2019-08-12 2021-02-18 罗欣药业(上海)有限公司 三环类化合物、其制备方法、中间体及应用
US12497412B2 (en) 2019-11-18 2025-12-16 Guangzhou Joyo Pharmatech Co., Ltd. Compound as highly selective ROS1 inhibitor and use thereof
WO2021108682A1 (en) 2019-11-27 2021-06-03 Turning Point Therapeutics, Inc. Combination therapy involving diaryl macrocyclic compounds
KR20220134522A (ko) * 2019-11-27 2022-10-05 터닝 포인트 테라퓨틱스, 인크. 디아릴 매크로시클릭 화합물을 수반하는 병용 요법
TW202134249A (zh) 2019-12-03 2021-09-16 美商特普醫葯公司 用於治療疾病的巨環
US12428433B2 (en) 2019-12-13 2025-09-30 Scinnohub Pharmaceutical Co., Ltd Fluorine-containing heterocyclic derivatives with macrocyclic structure and use thereof
CN113045575B (zh) * 2019-12-27 2022-06-17 成都倍特药业股份有限公司 一种化合物的制备方法及其中间体和中间体的制备方法
CN113527298B (zh) * 2020-04-17 2025-01-03 浙江海正药业股份有限公司 大环内酰胺类衍生物、及其制备方法和用途
CN113735856A (zh) * 2020-05-29 2021-12-03 百极弘烨(南通)医药科技有限公司 大环jak抑制剂及其应用
WO2021244609A1 (zh) * 2020-06-04 2021-12-09 成都倍特药业股份有限公司 具有大环结构的化合物及其用途
CN114073704B (zh) * 2020-08-14 2023-08-11 赛诺哈勃药业(成都)有限公司 具有大环结构的含氟并杂环衍生物的应用
IL301385A (en) * 2020-09-16 2023-05-01 Alumis Inc TYK2 inhibitors and their use
WO2022117090A1 (zh) * 2020-12-03 2022-06-09 成都科岭源医药技术有限公司 一种多环化合物及其制备方法和用途
CN114763360A (zh) * 2021-01-15 2022-07-19 广州百霆医药科技有限公司 手性大环化合物作为蛋白激酶抑制剂及其用途
CN117412970B (zh) * 2021-04-12 2025-12-30 成都倍特药业股份有限公司 含氟大环结构化合物的固体形态、制备方法和应用
WO2023025141A1 (zh) * 2021-08-23 2023-03-02 正大天晴药业集团股份有限公司 含有氨基的大环化合物在治疗trk激酶介导的肿瘤中的用途
CN113582994B (zh) * 2021-09-28 2022-02-11 北京鑫开元医药科技有限公司 具有trk激酶抑制活性的化合物、制备方法、组合物及其用途
CN116063326B (zh) * 2021-11-02 2025-08-05 赛诺哈勃药业(成都)有限公司 作为蛋白激酶调节剂的含氨基大环化合物
WO2023208244A1 (zh) * 2022-04-29 2023-11-02 南京明德新药研发有限公司 大环类化合物及其应用
AU2023339247A1 (en) 2022-09-07 2025-03-27 Suzhou Langrui Biopharmaceutical Co., Ltd. Macrocyclic imidazo[1,2-b]pyridazine derivative, preparation method therefor, and use thereof
CN115746023B (zh) * 2022-10-27 2024-08-09 复旦大学 一种作为蛋白激酶抑制剂的含吲唑结构的杂环大环化合物及其制备方法

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4838925A (en) 1986-04-25 1989-06-13 E. I. Du Pont De Nemours And Company Heterocyclic acyl sulfonamides
ES2021105B3 (es) 1987-03-07 1991-10-16 Bayer Ag Procedimiento para la obtencion de 5-amino-4,6-dihalogeno piridinas.
ES2149869T3 (es) 1993-03-25 2000-11-16 Upjohn Co Derivados de indol sustituidos por formil o ciano con actividad dopominergica.
KR100340159B1 (ko) 1993-12-07 2002-11-23 일라이 릴리 앤드 캄파니 단백질키나제c억제제
FR2746309B1 (fr) 1996-03-22 1998-04-17 Oreal Composition de teinture des fibres keratiniques contenant des pyrazolopyrimidineoxo ; leur utilisation pour la teinture comme coupleurs, procedes de teinture
RS49779B (sr) 1998-01-12 2008-06-05 Glaxo Group Limited, Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze
FR2793791B1 (fr) 1999-05-19 2002-01-25 Univ Paris 7 Denis Diderot Nouveaux composes inhibiteurs specifiques de phospholipases a2
WO2002010169A1 (en) 2000-07-31 2002-02-07 F. Hoffmann-La Roche Ag Piperazine derivatives
RU2275373C2 (ru) 2000-12-08 2006-04-27 Орто-Макнейл Фармасьютикал, Инк. Макрогетероциклические соединения
JP2004532834A (ja) 2001-03-23 2004-10-28 イーライ・リリー・アンド・カンパニー ヒスタミンh3受容体アンタゴニストである非イミダゾール系アリールアルキルアミン化合物、その製造および治療的使用
US7550470B2 (en) 2002-12-11 2009-06-23 Merck & Co. Inc. Substituted pyrazolo[1,5-A]pyrimidines as tyrosine kinase inhibitors
ES2668834T3 (es) 2008-09-08 2018-05-22 Merck Serono Sa Pirimidinas macrociclicas como inhibidores de proteína quinasas
SI2350075T1 (sl) * 2008-09-22 2014-06-30 Array Biopharma, Inc. Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji
CN102264736B (zh) * 2008-10-22 2013-08-14 阵列生物制药公司 作为TRK激酶抑制剂的取代的吡唑并[1,5-a]嘧啶化合物
BRPI0914404A2 (pt) 2008-10-31 2019-03-06 Genentech Inc "compostos, composição farmacêutica e método para tratar ou atenuar a gravidade de uma doença ou condição responsiva à inibição da atividade jak quinase em um paciente"
WO2010063487A1 (en) 2008-12-05 2010-06-10 Merz Pharma Gmbh & Co. Kgaa Pyrazolopyrimidines, a process for their preparation and their use as medicine
WO2010086040A1 (en) 2009-01-29 2010-08-05 Biomarin Iga, Ltd. Pyrazolo-pyrimidines for treatment of duchenne muscular dystrophy
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
WO2011045330A1 (en) 2009-10-13 2011-04-21 Tibotec Pharmaceuticals Macrocyclic integrase inhibitors
WO2011071725A1 (en) 2009-12-07 2011-06-16 Boehringer Ingelheim International Gmbh Heterocyclic compounds containing a pyrrolopyridine or benzimidazole core
US9150577B2 (en) 2009-12-07 2015-10-06 Boehringer Ingelheim International Gmbh Heterocyclic compounds containing an indole core
SA111320200B1 (ar) 2010-02-17 2014-02-16 ديبيوفارم اس ايه مركبات ثنائية الحلقة واستخداماتها كمثبطات c-src/jak مزدوجة
BR122019024201B1 (pt) 2010-05-20 2021-08-03 Array Biopharma Inc Composto macrocíclico como inibidores de trk quinase, seu uso, e composição farmacêutica
UY33597A (es) * 2010-09-09 2012-04-30 Irm Llc Compuestos y composiciones como inhibidores de la trk
WO2012034095A1 (en) 2010-09-09 2012-03-15 Irm Llc Compounds and compositions as trk inhibitors
WO2012075393A2 (en) 2010-12-02 2012-06-07 President And Fellows Of Harvard College Activators of proteasomal degradation and uses thereof
EP2508607A1 (en) 2011-04-07 2012-10-10 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
WO2013001310A1 (en) 2011-06-30 2013-01-03 Centro Nacional De Investigaciones Oncológicas (Cnio) Macrocyclic compounds and their use as cdk8 inhibitors
MX2014001945A (es) 2011-08-19 2014-03-27 Merck Sharp & Dohme Procedimiento e intermedios para la preparacion de macrolactamas.
WO2013045702A2 (en) 2011-09-29 2013-04-04 L'oreal Dye composition comprising a non-glycosyl iridoid compound and a specific nucleophile or an amino or thio polymer, dyeing process, and device therefor
WO2013045701A2 (en) 2011-09-29 2013-04-04 L'oreal Dyeing process using a composition comprising a glycosyl iridoid compound and a nucleophile or an amino or thio polymer, composition and devices therefor
MX347765B (es) 2011-09-30 2017-05-12 Oncodesign Sa Inhibidores macrociclicos de la quinasa flt3.
KR20140077963A (ko) 2011-10-20 2014-06-24 글락소스미스클라인 엘엘씨 시르투인 조절제로서의 치환된 비시클릭 아자-헤테로사이클 및 유사체
CA2863892C (en) * 2012-03-06 2016-08-30 Pfizer Inc. Macrocyclic derivatives for the treatment of proliferative diseases
DK2834243T3 (en) 2012-03-09 2018-07-23 Lexicon Pharmaceuticals Inc Pyrazole [1,5-a] pyrimidine-based compounds, compositions comprising them and methods for their use
RU2014140739A (ru) 2012-03-09 2016-04-27 Лексикон Фармасьютикалз, Инк. Соединения на основе имидазо[1, 2-b]пиридазина, композиции таких соединений и способы их применения
GB201205669D0 (en) 2012-03-30 2012-05-16 Agency Science Tech & Res Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof
EP2951174B1 (en) 2013-01-30 2017-04-26 Bayer Pharma Aktiengesellschaft Amino-substituted isothiazoles
CN105358534A (zh) 2013-04-23 2016-02-24 斯洛文尼亚莱柯制药股份有限公司 8-氯-1-甲基-苯并[d]吖庚因的新合成方法、新的中间体及其生产方法
JPWO2015012328A1 (ja) 2013-07-24 2017-03-02 武田薬品工業株式会社 複素環化合物
CN104513253A (zh) * 2013-10-01 2015-04-15 南京波尔泰药业科技有限公司 用于治疗增殖性疾病的大环化合物
WO2015073267A1 (en) 2013-11-15 2015-05-21 Calitor Sciences, Llc Substituted heteroaryl compounds and methods of use
WO2015112806A2 (en) * 2014-01-24 2015-07-30 Tp Therapeutics, Inc. Diaryl macrocycles as modulators of protein kinases
WO2016070241A1 (en) 2014-11-03 2016-05-12 Ctxt Pty Ltd Triazine compounds, compositions and synthesis
HUE067779T2 (hu) 2014-12-15 2024-11-28 Cmg Pharmaceutical Co Ltd Kondenzált gyûrûs heteroaril vegyületek és azok felhasználása TRK inhibitorokként
EP3259264B1 (en) 2015-02-20 2022-07-27 Rigel Pharmaceuticals, Inc. Gdf-8 inhibitors
US10329294B2 (en) 2015-03-12 2019-06-25 Merck Sharp & Dohme Corp. Pyrazolopyrimidine inhibitors of IRAK4 activity
US10155765B2 (en) 2015-03-12 2018-12-18 Merck Sharp & Dohme Corp. Carboxamide inhibitors of IRAK4 activity
JP2018520992A (ja) 2015-05-05 2018-08-02 バイエル ファーマ アクチエンゲゼルシャフト アミドで置換されているシクロヘキサン誘導体
RU2732405C2 (ru) 2015-07-02 2020-09-16 Тёрнинг Поинт Терапьютикс, Инк. Хиральные диарильные макроциклы в качестве модуляторов протеинкиназ
BR112018000297A2 (pt) 2015-07-06 2018-09-04 Tp Therapeutics Inc polimorfo de macrociclo de diarila
WO2017015367A1 (en) 2015-07-21 2017-01-26 Tp Therapeutics, Inc. Chiral diaryl macrocycles and uses thereof
EP3368039A1 (en) 2015-10-26 2018-09-05 The Regents of The University of Colorado, A Body Corporate Point mutations in trk inhibitor-resistant cancer and methods relating to the same
JP7086395B2 (ja) 2016-03-04 2022-06-20 ヴァンダービルト ユニバーシティー 置換インドールMcl-1阻害剤
AU2017302019A1 (en) 2016-07-28 2019-02-07 Turning Point Therapeutics, Inc. Macrocycle kinase inhibitors
WO2018112027A1 (en) 2016-12-14 2018-06-21 Development Center For Biotechnology Antibody-drug conjugates and uses thereof
TWI808958B (zh) 2017-01-25 2023-07-21 美商特普醫葯公司 涉及二芳基巨環化合物之組合療法
PT3658148T (pt) 2017-07-28 2024-08-26 Turning Point Therapeutics Inc Compostos macrocíclicos e utilizações dos mesmos

Also Published As

Publication number Publication date
WO2017004342A1 (en) 2017-01-05
EP3317285B1 (en) 2021-01-27
RU2018103907A3 (enExample) 2019-10-07
US20180186813A1 (en) 2018-07-05
KR20180023970A (ko) 2018-03-07
ES2864839T3 (es) 2021-10-14
EP3317285A4 (en) 2019-02-27
US11008337B2 (en) 2021-05-18
RU2018103907A (ru) 2019-08-05
AU2020217336A1 (en) 2020-08-27
CA2989327A1 (en) 2017-01-05
IL256377A (en) 2018-02-28
CN107735399B (zh) 2021-01-26
JP6871903B2 (ja) 2021-05-19
JP2018519343A (ja) 2018-07-19
US10316044B2 (en) 2019-06-11
MX2017017097A (es) 2018-05-23
KR102599788B1 (ko) 2023-11-07
AU2016287568B2 (en) 2020-08-20
AU2016287568A1 (en) 2018-01-04
CN107735399A (zh) 2018-02-23
EP3317285A1 (en) 2018-05-09
RU2732405C2 (ru) 2020-09-16
US20190284209A1 (en) 2019-09-19

Similar Documents

Publication Publication Date Title
CN107735399B (zh) 作为蛋白质激酶的调节剂的手性二芳基大环
CN111511746B (zh) 用于治疗疾病的巨环化合物
WO2024041606A1 (zh) 具有抗kras突变肿瘤活性的化合物
CN104507926B (zh) 丝氨酸/苏氨酸激酶抑制剂
TW202430162A (zh) 具有抗kras突變腫瘤活性的化合物
TW202346297A (zh) 具有抗kras突變腫瘤活性的化合物
TW202525800A (zh) Ras抑制劑
TW201815799A (zh) 巨環激酶抑制劑
CN106573906A (zh) 哌啶‑二酮衍生物
CN106536503A (zh) 一种酪氨酸激酶抑制剂及其用途
TW201930313A (zh) 巨環激酶抑制劑及其用途
CN109745321B (zh) 包含fgfr4抑制剂的药物组合物
TW202112783A (zh) 三環類化合物及其用途
TW202413377A (zh) 吲唑巨環化合物及其用途
WO2025218798A1 (zh) Kras g12d降解剂及其制备方法和应用
WO2020257165A1 (en) Macrocycles for use in treating disease
WO2025148870A1 (zh) Ras抑制剂
CN114555597B (zh) 异柠檬酸脱氢酶(idh)抑制剂
CN114853679A (zh) 一种苯并咪唑类enl蛋白抑制剂及其制备方法和用途
KR20210146320A (ko) 신규 아자인돌 유도체
HK1230591B (en) Tyrosine kinase inhibitor and uses thereof
HK1231407B (en) Diaryl macrocycles as modulators of protein kinases
HK1210166A1 (en) Fused tricyclic amide compounds as multiple kinase inhibitors
HK1210166B (en) Fused tricyclic amide compounds as multiple kinase inhibitors