CN108137582A - 作为双重DYRK1/CLK1抑制剂的新的吡咯并[2,3-d]嘧啶衍生物 - Google Patents

作为双重DYRK1/CLK1抑制剂的新的吡咯并[2,3-d]嘧啶衍生物 Download PDF

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Publication number
CN108137582A
CN108137582A CN201680058179.3A CN201680058179A CN108137582A CN 108137582 A CN108137582 A CN 108137582A CN 201680058179 A CN201680058179 A CN 201680058179A CN 108137582 A CN108137582 A CN 108137582A
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China
Prior art keywords
formula
methyl
pyrrolo
compound
alkylene
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Withdrawn
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CN201680058179.3A
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English (en)
Chinese (zh)
Inventor
A·菲乌马纳
N·弗洛派
S·雷
D·沃姆斯利
A·科斯基
M·F·博布里奇
F·H·克鲁扎勒圭
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Furnalis R&d Co ltd
Laboratoires Servier SAS
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Furnalis R&d Co ltd
Laboratoires Servier SAS
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Publication of CN108137582A publication Critical patent/CN108137582A/zh
Withdrawn legal-status Critical Current

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    • 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
    • C07D487/02—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 two hetero rings
    • C07D487/04—Ortho-condensed 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
    • A61K31/435—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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 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
    • 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
    • A61K31/435—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
    • 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
    • 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
    • A61K31/535—Heterocyclic 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201680058179.3A 2015-09-30 2016-09-30 作为双重DYRK1/CLK1抑制剂的新的吡咯并[2,3-d]嘧啶衍生物 Withdrawn CN108137582A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR1559259A FR3041640B1 (fr) 2015-09-30 2015-09-30 NOUVEAUX DERIVES DE PYRROLO[2,3-d]PYRIMIDINE, LEUR PROCEDE DE PREPRATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
FR15/59259 2015-09-30
PCT/EP2016/073403 WO2017055533A1 (en) 2015-09-30 2016-09-30 New pyrrolo[2,3-d]pyrimidine derivatives as dual dyrk1/clk1 inhibitors

Publications (1)

Publication Number Publication Date
CN108137582A true CN108137582A (zh) 2018-06-08

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CN201680058179.3A Withdrawn CN108137582A (zh) 2015-09-30 2016-09-30 作为双重DYRK1/CLK1抑制剂的新的吡咯并[2,3-d]嘧啶衍生物

Country Status (26)

Country Link
US (1) US20180273538A1 (enExample)
EP (1) EP3356364A1 (enExample)
JP (1) JP2018533552A (enExample)
KR (1) KR20180054856A (enExample)
CN (1) CN108137582A (enExample)
AU (1) AU2016333508A1 (enExample)
BR (1) BR112018005851A2 (enExample)
CA (1) CA2999937A1 (enExample)
CL (1) CL2018000786A1 (enExample)
CO (1) CO2018003466A2 (enExample)
CR (1) CR20180176A (enExample)
CU (1) CU20180027A7 (enExample)
DO (1) DOP2018000082A (enExample)
EA (1) EA201890820A1 (enExample)
EC (1) ECSP18023286A (enExample)
FR (1) FR3041640B1 (enExample)
HK (1) HK1255467A1 (enExample)
IL (1) IL258231A (enExample)
MA (1) MA43021A (enExample)
MX (1) MX2018003861A (enExample)
NI (1) NI201800042A (enExample)
PE (1) PE20190337A1 (enExample)
PH (1) PH12018500605A1 (enExample)
SV (1) SV2018005656A (enExample)
TN (1) TN2018000087A1 (enExample)
WO (1) WO2017055533A1 (enExample)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110407744A (zh) * 2019-08-13 2019-11-05 上海毕得医药科技有限公司 一种1-(4-氨基吡啶-2-基)乙酮的合成方法
CN113164476A (zh) * 2018-09-28 2021-07-23 代表亚利桑那大学的亚利桑那校董会 Dyrk1/clk的小分子抑制剂及其用途
CN115785134A (zh) * 2022-10-28 2023-03-14 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用
CN116783198A (zh) * 2020-12-02 2023-09-19 百极弘烨（广东）医药科技有限公司 螺环jak抑制剂、含其的药物组合物及其应用

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20180094A1 (ar) 2017-10-18 2019-04-18 Hk Inno N Corp مركب حلقي غير متجانس كمثبط بروتين كيناز
KR102054910B1 (ko) * 2017-12-19 2019-12-12 한림제약(주) 피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
CN113227089B (zh) 2018-10-31 2024-07-05 吉利德科学公司 作为hpk1抑制剂的取代的6-氮杂苯并咪唑化合物
CN117105933A (zh) 2018-10-31 2023-11-24 吉利德科学公司 具有hpk1抑制活性的取代的6-氮杂苯并咪唑化合物
KR102195348B1 (ko) 2018-11-15 2020-12-24 에이치케이이노엔 주식회사 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물
EP3972695A1 (en) 2019-05-23 2022-03-30 Gilead Sciences, Inc. Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors
AR120799A1 (es) * 2019-12-20 2022-03-16 Hoffmann La Roche 2-[4-cloro-6-[2-[4-[[4-(hidroximetil)-1-piperidil]metil]fenil]etinil]-1-oxoisoindolin-2-il]-2-(6,7-dihidro-5h-pirrolo[1,2-c]imidazol-1-il)-n-tiazol-2-il-acetamida como inhibidor de egfr
US20240261297A1 (en) * 2021-05-20 2024-08-08 St. John's Cancer Institute Anti-cdk inhibitors for cancer treatment
TW202330533A (zh) * 2021-10-12 2023-08-01 美商生物銜接醫療公司 7h-吡咯并[2,3-d]嘧啶及其製備及用途
US12134625B2 (en) 2021-10-12 2024-11-05 Biosplice Therapeutics, Inc. Pyrrolo[2,1-f][1,2,4]triazines and preparation and uses thereof
US20230192686A1 (en) * 2021-10-12 2023-06-22 Biosplice Therapeutics, Inc. 1h-pyrrolo[2,3-b]pyridines and preparation and uses thereof
WO2023110843A1 (en) * 2021-12-15 2023-06-22 Almirall, S.A. Heterobicyclic derivatives as itk inhibitors
CN116621843B (zh) * 2022-06-13 2024-05-24 四川大学华西医院 一种dna甲基转移酶1抑制剂及其制备方法和用途

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2006343808B2 (en) 2005-05-20 2012-03-29 Mirati Therapeutics, Inc. Inhibitors of VEGF receptor and HGF receptor signaling
EP1948659A1 (en) 2005-10-13 2008-07-30 Glaxo Group Limited Pyrrolopyrimidine derivatives as syk inhibitors
EP2007767B1 (en) 2006-03-11 2011-11-02 Vernalis (R&D) Ltd Pyrrolopyrimidine derivatives used as hsp90 inhibitors
FR2912744B1 (fr) * 2007-02-16 2012-09-07 Centre Nat Rech Scient Composes pyrrolo°2,3-b!pyridine,composes azaindoles utiles dans la synthese de ces composes pyrrolo°2,3-b!pyridine, leurs procedes de fabrication et leurs utilisations.
AR070127A1 (es) 2008-01-11 2010-03-17 Novartis Ag Pirrolo - pirimidinas y pirrolo -piridinas
KR20150027267A (ko) * 2012-06-29 2015-03-11 화이자 인코포레이티드 LRRK2 억제제로서의 4-(치환된-아미노)-7H-피롤로[2,3-d]피리미딘
US9695171B2 (en) * 2013-12-17 2017-07-04 Pfizer Inc. 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 inhibitors

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113164476A (zh) * 2018-09-28 2021-07-23 代表亚利桑那大学的亚利桑那校董会 Dyrk1/clk的小分子抑制剂及其用途
US12054483B2 (en) 2018-09-28 2024-08-06 Arizona Board Of Regents On Behalf Of The University Of Arizona Small molecule inhibitors of DYRK/CLK and uses thereof
CN110407744A (zh) * 2019-08-13 2019-11-05 上海毕得医药科技有限公司 一种1-(4-氨基吡啶-2-基)乙酮的合成方法
CN116783198A (zh) * 2020-12-02 2023-09-19 百极弘烨（广东）医药科技有限公司 螺环jak抑制剂、含其的药物组合物及其应用
CN116783198B (zh) * 2020-12-02 2025-10-21 广东弘烨医药科技有限公司 螺环jak抑制剂、含其的药物组合物及其应用
CN115785134A (zh) * 2022-10-28 2023-03-14 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用
CN115785134B (zh) * 2022-10-28 2023-08-29 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用
WO2024087419A1 (zh) * 2022-10-28 2024-05-02 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用

Also Published As

Publication number Publication date
CR20180176A (es) 2018-05-31
MA43021A (fr) 2018-08-08
BR112018005851A2 (pt) 2018-10-09
CA2999937A1 (en) 2017-04-06
SV2018005656A (es) 2018-08-10
CO2018003466A2 (es) 2018-07-10
KR20180054856A (ko) 2018-05-24
NI201800042A (es) 2018-06-21
WO2017055533A1 (en) 2017-04-06
ECSP18023286A (es) 2018-04-30
DOP2018000082A (es) 2018-10-15
PE20190337A1 (es) 2019-03-07
PH12018500605A1 (en) 2018-09-24
TN2018000087A1 (en) 2019-07-08
FR3041640A1 (enExample) 2017-03-31
MX2018003861A (es) 2018-08-16
EA201890820A1 (ru) 2018-10-31
AU2016333508A1 (en) 2018-04-12
CL2018000786A1 (es) 2018-09-28
JP2018533552A (ja) 2018-11-15
US20180273538A1 (en) 2018-09-27
FR3041640B1 (fr) 2019-05-17
CU20180027A7 (es) 2018-07-05
HK1255467A1 (zh) 2019-08-16
EP3356364A1 (en) 2018-08-08
IL258231A (en) 2018-05-31

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