KR20220024605A - 아미노피리미딘 아미드 자가포식 억제제 및 이의 사용 방법 - Google Patents

아미노피리미딘 아미드 자가포식 억제제 및 이의 사용 방법 Download PDF

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KR20220024605A
KR20220024605A KR1020227001491A KR20227001491A KR20220024605A KR 20220024605 A KR20220024605 A KR 20220024605A KR 1020227001491 A KR1020227001491 A KR 1020227001491A KR 20227001491 A KR20227001491 A KR 20227001491A KR 20220024605 A KR20220024605 A KR 20220024605A
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amino
alkyl
cycloalkyl
propyl
methyl
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Korean (ko)
Inventor
다니엘 엘. 플린
유 미 안
티모시 콜드웰
라크쉬미나라야나 보게티
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데시페라 파마슈티칼스, 엘엘씨.
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Publication of KR20220024605A publication Critical patent/KR20220024605A/ko
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48Two nitrogen atoms
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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    • A61K31/47Quinolines; Isoquinolines
    • A61K31/475Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
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    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
KR1020227001491A 2019-06-17 2020-06-16 아미노피리미딘 아미드 자가포식 억제제 및 이의 사용 방법 Pending KR20220024605A (ko)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201962862469P 2019-06-17 2019-06-17
US201962862470P 2019-06-17 2019-06-17
US62/862,469 2019-06-17
US62/862,470 2019-06-17
US201962911739P 2019-10-07 2019-10-07
US201962911740P 2019-10-07 2019-10-07
US62/911,739 2019-10-07
US62/911,740 2019-10-07
PCT/US2020/037906 WO2020257180A1 (en) 2019-06-17 2020-06-16 Aminopyrimidine amide autophagy inhibitors and methods of use thereof

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KR20220024605A true KR20220024605A (ko) 2022-03-03

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US (3) US11590134B2 (https=)
EP (1) EP3983081B1 (https=)
JP (2) JP7626722B2 (https=)
KR (1) KR20220024605A (https=)
CN (3) CN114258318B (https=)
AU (2) AU2020297422B2 (https=)
BR (1) BR112021025544A2 (https=)
CA (1) CA3143489A1 (https=)
CL (1) CL2021003356A1 (https=)
CO (1) CO2022000260A2 (https=)
IL (2) IL325201A (https=)
MA (1) MA56191A (https=)
MX (2) MX2021015628A (https=)
PE (1) PE20221083A1 (https=)
PH (1) PH12021553166A1 (https=)
TW (1) TWI904091B (https=)
WO (1) WO2020257180A1 (https=)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL276398B2 (en) 2018-01-31 2026-03-01 Deciphera Pharmaceuticals Llc Combination therapy for mastocytosis
EP3938363A1 (en) 2019-03-11 2022-01-19 Teva Pharmaceuticals International GmbH Solid state forms of ripretinib
MX2021013662A (es) 2019-05-10 2022-03-11 Deciphera Pharmaceuticals Llc Inhibidores de la autofagia de heteroarilaminopirimidina amida y metodos de uso de estos.
EP3966207B1 (en) 2019-05-10 2023-11-01 Deciphera Pharmaceuticals, LLC Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof
IL325201A (en) 2019-06-17 2026-02-01 Deciphera Pharmaceuticals Llc Aminopyrimidine amide autophagy inhibitors and methods of using them
LT4013412T (lt) 2019-08-12 2026-03-25 Deciphera Pharmaceuticals, Llc Ripretinibas, skirtas virškinamojo trakto stromos navikų gydymui
IL326597A (en) 2019-10-07 2026-04-01 Contineum Therapeutics Inc Muscarinic M1 acetylcholine receptor antagonists
US11752149B2 (en) 2019-12-02 2023-09-12 Pipeline Therapeutics, Inc. Muscarinic acetylcholine M1 receptor antagonists
CN115243681B (zh) 2019-12-30 2024-08-16 德西费拉制药有限责任公司 1-(4-溴-5-(1-乙基-7-(甲氨基)-2-侧氧基-1,2-二氢-1,6-萘啶-3-基)-2-氟苯基)-3-苯基脲的组合物
KR20220153582A (ko) 2020-02-14 2022-11-18 솔크 인스티튜트 포 바이올로지칼 스터디즈 마크로시클릭 ulk1/2 억제제
MX2023005747A (es) 2020-11-18 2023-07-28 Deciphera Pharmaceuticals Llc Inhibidores de gcn2 y perk quinasas y metodos de uso de los mismos.
KR20240113496A (ko) 2021-12-03 2024-07-22 데시페라 파마슈티칼스, 엘엘씨. Gcn2 및 perk 키나아제 억제제로서의 헤테로고리 화합물
US12319655B2 (en) 2021-12-09 2025-06-03 Deciphera Pharmaceuticals, Llc RAF kinase inhibitors and methods of use thereof
WO2023215494A1 (en) * 2022-05-04 2023-11-09 Erasca, Inc. Thiophene ulk1/2 inhibitors and their use thereof
WO2024229322A1 (en) * 2023-05-04 2024-11-07 Erasca, Inc. Thiophene ulk1/2 inhibitors and their use thereof
WO2025045182A1 (zh) * 2023-09-01 2025-03-06 深圳众格生物科技有限公司 Ulk1抑制剂及其制备方法和用途

Family Cites Families (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19824922A1 (de) 1998-06-04 1999-12-09 Boehringer Ingelheim Pharma Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
US6262088B1 (en) 1998-11-19 2001-07-17 Berlex Laboratories, Inc. Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
GB9910807D0 (en) 1999-05-10 1999-07-07 Prometic Biosciences Limited Novel detoxification agents and their use
US6906067B2 (en) 1999-12-28 2005-06-14 Bristol-Myers Squibb Company N-heterocyclic inhibitors of TNF-α expression
WO2001085700A2 (en) 2000-05-08 2001-11-15 Janssen Pharmaceutica N.V. Hiv replication inhibiting pyrimidines and triazines
PE20030008A1 (es) 2001-06-19 2003-01-22 Bristol Myers Squibb Co Inhibidores duales de pde 7 y pde 4
JP2005500294A (ja) 2001-06-19 2005-01-06 ブリストル−マイヤーズ スクイブ カンパニー ホスホジエステラーゼ7に対するピリミジン阻害剤
US20030139435A1 (en) 2001-06-26 2003-07-24 Gulzar Ahmed N-heterocyclic inhibitors of TNF-alpha expression
WO2003030909A1 (en) 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
EP1453516A2 (de) 2001-10-17 2004-09-08 Boehringer Ingelheim Pharma GmbH & Co.KG 5-substituierte 4-amino-2-phenylamino-pyrimdinderivate und ihre verwendung als beta-amyloid modulatoren
ATE407678T1 (de) 2001-10-17 2008-09-15 Boehringer Ingelheim Pharma Pyrimidinderivate, arzneimittel enthaltend diese verbindungen, deren verwendung und verfahren zu ihrer herstellung
JP4072615B2 (ja) 2002-03-05 2008-04-09 独立行政法人産業技術総合研究所 配位子を有する複素環化合物及びその製造方法、及びこの複素環化合物を用いる金属元素の固定化膜
BR0316680A (pt) 2002-11-28 2005-10-18 Schering Ag Pirimidinas inibidoras de chk, pdk e akt, sua produção e uso como agentes farmacêuticos
US7202257B2 (en) 2003-12-24 2007-04-10 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7279576B2 (en) 2002-12-31 2007-10-09 Deciphera Pharmaceuticals, Llc Anti-cancer medicaments
US7144911B2 (en) 2002-12-31 2006-12-05 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
CL2004000303A1 (es) 2003-02-20 2005-04-08 Tibotec Pharm Ltd Compuestos derivados de pirimidinas y triazinas; proceso de preparacion; composicion farmaceutica; y su uso para inhibir la replicacion del vih.
EP1781659B1 (en) 2003-07-16 2008-11-05 Janssen Pharmaceutica N.V. Triazolopyrimidine derivatives as glycogen synthase kinase 3 inhibitors
BRPI0413018B8 (pt) 2003-07-30 2021-05-25 Rigel Pharmaceuticals Inc composto, e, uso de um composto
WO2005013996A2 (en) 2003-08-07 2005-02-17 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents
EP1763514A2 (en) 2004-05-18 2007-03-21 Rigel Pharmaceuticals, Inc. Cycloalkyl substituted pyrimidinediamine compounds and their uses
EA011671B1 (ru) 2004-06-04 2009-04-28 Арена Фармасьютикалз, Инк. Замещенные производные арила и гетероарила в качестве модуляторов метаболизма и для профилактики и лечения связанных с ним расстройств
GB0512324D0 (en) 2005-06-16 2005-07-27 Novartis Ag Organic compounds
WO2006071940A2 (en) 2004-12-23 2006-07-06 Deciphera Pharmaceuticals, Llc Enzyme modulators and treatments
AU2005324024B2 (en) 2005-01-07 2011-02-17 F. Hoffmann-La Roche Ag [4-(Heteroaryl) piperazin-1-yl]-(2,5-substituted -phenyl)methanone derivatives as glycine transporter 1 (GlyT-1) inhibitors for the treatment of neurological and neuropsychiatric disorders
WO2006128172A2 (en) 2005-05-26 2006-11-30 Synta Pharmaceuticals Corp. Method for treating b cell regulated autoimmune disorders
WO2006128129A2 (en) 2005-05-26 2006-11-30 Synta Pharmaceuticals Corp. Method for treating cancer
US8193206B2 (en) 2005-06-14 2012-06-05 Taigen Biotechnology Co., Ltd. Pyrimidine compounds
US8748627B2 (en) 2006-02-15 2014-06-10 Abbvie Inc. Acetyl-CoA carboxylase (ACC) inhibitors and their use in diabetes, obesity and metabolic syndrome
US20090312321A1 (en) 2006-05-15 2009-12-17 Irm Llc Compositions and methods for fgf receptor kinases inhibitors
RU2008152195A (ru) 2006-06-15 2010-07-20 БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) 2-анилино-4-(гетероциклил)аминопиримидины, как ингибиторы протеинкиназы с-альфа
US7897762B2 (en) 2006-09-14 2011-03-01 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of proliferative diseases
US8188113B2 (en) 2006-09-14 2012-05-29 Deciphera Pharmaceuticals, Inc. Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
US7790756B2 (en) 2006-10-11 2010-09-07 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases
US20100298557A1 (en) 2006-12-28 2010-11-25 Taisho Pharmaceutical Co., Ltd Pyrazolopyrimidine compound
KR20100014811A (ko) 2007-04-20 2010-02-11 데시페라 파마슈티칼스, 엘엘씨. 골수증식성 질환 및 기타 증식성 질환의 치료에 유용한 키나제 억제제
CN101910151A (zh) 2007-10-22 2010-12-08 先灵公司 双环杂环衍生物及其作为gpr119活性调节剂的用途
WO2009122180A1 (en) 2008-04-02 2009-10-08 Medical Research Council Pyrimidine derivatives capable of inhibiting one or more kinases
UY31929A (es) 2008-06-25 2010-01-05 Irm Llc Compuestos y composiciones como inhibidores de cinasa
JP2011525930A (ja) 2008-06-26 2011-09-29 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 Akt活性の阻害剤
TWI546290B (zh) 2008-06-27 2016-08-21 賽基艾維洛米斯研究股份有限公司 雜芳基化合物及其用途
US8338439B2 (en) 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
CN102256493A (zh) 2008-10-29 2011-11-23 迪赛孚尔制药有限公司 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物
WO2010111406A2 (en) 2009-03-24 2010-09-30 Myriad Pharmaceuticals, Inc. Compounds and therapeutic uses thereof
US8410126B2 (en) 2009-05-29 2013-04-02 Boehringer Ingelheim International Gmbh Pyrimidine inhibitors of PKTK2
TW201100441A (en) 2009-06-01 2011-01-01 Osi Pharm Inc Amino pyrimidine anticancer compounds
PH12012500097A1 (en) * 2009-07-21 2011-01-27 Shanghai Inst Organic Chem Potent small molecule inhibitors of autophagy, and methods of use thereof
WO2011075517A1 (en) 2009-12-17 2011-06-23 Merck Sharp & Dohme Corp. Aminopyrimidines as syk inhibitors
EP2519664A4 (en) 2009-12-30 2014-03-12 Avila Therapeutics Inc LIGAND-RELATED COVALENTS MODIFYING A PROTEIN
BR112012027743A2 (pt) 2010-04-29 2017-03-14 Deciphera Pharmaceuticals Llc ciclopropil dicarboxamidas e análogos exibindo atividades anticâncer e antiproliferativas
EP2563773A1 (en) 2010-04-29 2013-03-06 Deciphera Pharmaceuticals, LLC Pyridone amides and analogs exhibiting anti-cancer and anti-proliferative activites
PT2576541T (pt) 2010-06-04 2016-07-08 Hoffmann La Roche Derivados de aminopirimidina como moduladores de lrrk2
WO2012033195A1 (ja) 2010-09-10 2012-03-15 京都薬品工業株式会社 複素環化合物
HRP20172006T1 (hr) 2010-11-10 2018-02-09 Genentech, Inc. Derivati pirazol-aminopiridina kao lrrk2-modulatori
EP2675793B1 (en) 2011-02-17 2018-08-08 Cancer Therapeutics Crc Pty Limited Fak inhibitors
CN103781780B (zh) 2011-07-28 2015-11-25 赛尔佐姆有限公司 作为jak抑制剂的杂环基嘧啶类似物
BR112014012407A2 (pt) 2011-11-22 2017-06-06 Deciphera Pharmaceuticals Llc amidas de piridona e análogos exibindo propriedades anti-câncer e anti-proliferativas
CN103958482B (zh) 2011-11-29 2017-06-09 健泰科生物技术公司 作为lrrk2调节剂的氨基嘧啶衍生物
BR112014009717B1 (pt) 2011-11-29 2022-06-14 Genentech, Inc Derivados de 2-(fenil ou pirid-3-il)aminopirimidina, seus usos, e composição farmacêutica
EP2785381B1 (en) 2011-11-30 2016-05-18 F.Hoffmann-La Roche Ag Fluorine-18 and carbon-11 labeled radioligands for positron emission tomography (pet) imaging for lrrk2
CN103159736B (zh) * 2011-12-10 2015-05-13 通化济达医药有限公司 取代的吡唑激酶抑制剂
AR090151A1 (es) 2012-03-07 2014-10-22 Lilly Co Eli Compuestos inhibidores de raf
US9187474B2 (en) 2012-03-07 2015-11-17 Deciphera Pharmaceuticals, Llc Raf inhibitor compounds
GB201204384D0 (en) 2012-03-13 2012-04-25 Univ Dundee Anti-flammatory agents
US8461179B1 (en) 2012-06-07 2013-06-11 Deciphera Pharmaceuticals, Llc Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
US20140073634A1 (en) 2012-08-24 2014-03-13 Institute For Applied Cancer Science/The University of Texas MD Anderson Cancer Center Heterocyclic modulators of hif activity for treatment of disease
WO2014078378A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
DK2930167T3 (en) 2012-12-06 2019-02-25 Kbp Biosciences Co Ltd INDOLINO DERIVATIVE AS A TYROSINKINASE INHIBITOR
CA2903285C (en) 2013-03-15 2021-05-11 Deciphera Pharmaceuticals, Llc 2-aminopyrimidin-6-ones and analogs exhibiting anti-cancer and anti-proliferative activities
US9133183B2 (en) 2013-03-15 2015-09-15 Deciphera Pharmaceuticals, Llc Imidazolidinones and analogs exhibiting anti-cancer and anti-proliferative activities
RU2769607C2 (ru) 2013-03-15 2022-04-04 ДЕСИФЕРА ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи N-ацил-N'-(пиридин-2-ил) карбамиды и их аналоги, проявляющие противораковую и антипролиферативную активность
WO2014145004A1 (en) 2013-03-15 2014-09-18 Deciphera Pharmaceuticals, Llc Pyridone amides and analogs exhibiting anti-cancer and anti-proliferative activities
US9193719B2 (en) 2013-03-15 2015-11-24 Deciphera Pharmaceuticals, Llc 1,2,4-triazol-5-ones and analogs exhibiting anti-cancer and anti-proliferative activities
US9309224B2 (en) 2013-03-15 2016-04-12 Deciphera Pharmaceuticals, Llc. N-acyl-N′-(pyridin-2-yl) ureas and analogs exhibiting anti-cancer and anti-proliferative activities
CN103242341B (zh) 2013-04-19 2015-12-09 中国科学院广州生物医药与健康研究院 噻吩并2,4取代嘧啶类化合物及其药物组合物与应用
EP3019491A4 (en) 2013-07-09 2016-12-21 Dana Farber Cancer Inst Inc KINASEHEMMER FOR THE TREATMENT OF DISEASES
WO2015039613A1 (zh) 2013-09-18 2015-03-26 北京韩美药品有限公司 抑制btk和/或jak3激酶活性的化合物
KR101879422B1 (ko) 2013-09-18 2018-07-17 베이징 한미 파마슈티컬 컴퍼니 리미티드 Btk 및/또는 jak3 키나제의 활성을 억제하는 화합물
MX378288B (es) 2013-10-18 2025-03-10 Eisai R&D Man Co Ltd Inhibidores de pirimidina del fgfr4.
BR112016008632A8 (pt) 2013-10-21 2020-03-17 Merck Patent Gmbh compostos de heteroarila como inibidores de btk, seus usos, e composição farmacêutica
US9457019B2 (en) 2013-11-07 2016-10-04 Deciphera Pharmaceuticals, Llc Methods for inhibiting tie-2 kinase useful in the treatment of cancer
WO2015123722A1 (en) * 2014-02-19 2015-08-27 Bionomics Limited Inhibitors
US20150284341A1 (en) 2014-04-07 2015-10-08 Catylix, Inc. Fluoroalkyl-substituted derivatives of pyridine, pyrimidine, and pyrazine
DK3185868T3 (da) 2014-08-25 2022-05-23 Salk Inst For Biological Studi Hidtil ukendte ULK1-inhibitorer og fremgangsmåder til anvendelse af samme
CN105399685B (zh) 2014-09-16 2018-05-22 深圳微芯生物科技有限责任公司 作为选择性jak3和/或jak1激酶抑制剂的芳杂环化合物的制备方法及其应用
EP3056202A1 (en) 2015-02-16 2016-08-17 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Benzopyrrolidone derivatives possessing antiviral and anticancer properties
JP2018510140A (ja) 2015-02-25 2018-04-12 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft アルキニルアルコール及び使用方法
WO2017023899A1 (en) 2015-08-02 2017-02-09 H. Lee Moffitt Cancer Center & Research Institute Inhibitors of ack1/tnk2 tyrosine kinase
US10738016B2 (en) 2015-10-13 2020-08-11 H. Lee Moffitt Cancer Center And Research Institute, Inc. BRD4-kinase inhibitors as cancer therapeutics
EP3371164B1 (en) * 2015-11-06 2022-03-16 Neurocrine Biosciences, Inc. N-[2-(1-benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine-1-carboxamide derivatives and related compounds as muscarinic receptor 4 (m4) antagonists for treating neurological diseases
US11028080B2 (en) 2016-03-11 2021-06-08 Denali Therapeutics Inc. Substituted pyrimidines as LRKK2 inhibitors
CN108239069B (zh) * 2016-12-26 2021-01-05 南京药捷安康生物科技有限公司 一种用于成纤维细胞生长因子受体的抑制剂及其用途
BR112019017741A2 (pt) 2017-02-28 2020-04-07 Dana Farber Cancer Inst Inc usos de pirimidopirimidinonas como inibidores de sik
CA3065365C (en) 2017-05-30 2025-09-16 Deciphera Pharmaceuticals, Llc USE OF 1-[4-BROMO-5-[1-ETHYL-7-(METHYLAMINO)-2-OXO-1,2-DIHYDRO-1,6-NAPHTHYRIDINE-3-YL]-2-FLUOROPHENYL]-3-PHENYLUREA AND ITS ANALOGUES FOR THE TREATMENT OF CANCERS ASSOCIATED WITH GENETIC ABNORMALITIES IN THE PLATELET-DERIVED GROWTH FACTOR ALPHA RECEPTOR
CN109535132B (zh) 2017-09-21 2021-07-20 北京赛特明强医药科技有限公司 2-取代吡唑氨基-4-取代氨基-5-嘧啶甲酰胺类化合物、组合物及其应用
IL276398B2 (en) 2018-01-31 2026-03-01 Deciphera Pharmaceuticals Llc Combination therapy for mastocytosis
DK3774736T3 (da) 2018-03-27 2023-01-30 Neuropore Therapies Inc Forbindelser som modulatorer af TLR2-signalering
ES3032793T3 (en) 2018-04-10 2025-07-24 Neuropore Therapies Inc Tri-substituted aryl and heteroaryl derivatives as modulators of pi3-kinase and autophagy pathways
SMT202500389T1 (it) 2018-12-28 2025-11-10 Deciphera Pharmaceuticals Llc Inibitori di csf1r per l'uso nel trattamento di tumori tenosinoviali a cellule giganti
EP3966200A1 (en) 2019-05-10 2022-03-16 Cersci Therapeutics, Inc. Manufacturing methods and polymorphs of a thiazoline anti-hyperalgesic agent
MX2021013662A (es) 2019-05-10 2022-03-11 Deciphera Pharmaceuticals Llc Inhibidores de la autofagia de heteroarilaminopirimidina amida y metodos de uso de estos.
EP3966207B1 (en) 2019-05-10 2023-11-01 Deciphera Pharmaceuticals, LLC Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof
CR20210556A (es) 2019-05-10 2021-12-17 Janssen Biotech Inc Quelantes macrocíclicos y métodos de uso de estos
IL325201A (en) 2019-06-17 2026-02-01 Deciphera Pharmaceuticals Llc Aminopyrimidine amide autophagy inhibitors and methods of using them
JP2022552655A (ja) 2019-10-07 2022-12-19 キャリーオペ,インク. Gpr119アゴニスト
US12458630B2 (en) 2020-01-14 2025-11-04 The Regents Of The University Of California Combination therapy for cancer
WO2023108110A2 (en) 2021-12-10 2023-06-15 Verastem, Inc. Combination therapy for treating abnormal cell growth

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