CN112638405A - 用于治疗神经退行性疾病的对rip激酶的抑制 - Google Patents

用于治疗神经退行性疾病的对rip激酶的抑制 Download PDF

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Publication number
CN112638405A
CN112638405A CN201980057467.0A CN201980057467A CN112638405A CN 112638405 A CN112638405 A CN 112638405A CN 201980057467 A CN201980057467 A CN 201980057467A CN 112638405 A CN112638405 A CN 112638405A
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ripk2
disease
ripk
inhibitor
nod2
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Chinese (zh)
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李瑟期
高汉锡
T·M·道森
M·G·蓬佩尔
金动勋
吴裕敏
权升焕
朴勇柱
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Johns Hopkins University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/44Non 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4709Non-condensed quinolines and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/5025Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/504Pyridazines; Hydrogenated pyridazines forming part of bridged ring systems
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/529Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
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    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00Drugs for disorders of the nervous system
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    • C12YENZYMES
    • C12Y207/00Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/10Protein-tyrosine kinases (2.7.10)
    • C12Y207/10002Non-specific protein-tyrosine kinase (2.7.10.2), i.e. spleen tyrosine kinase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5058Neurological cells
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701Details
    • G01N2333/4709Amyloid plaque core protein
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2440/00Post-translational modifications [PTMs] in chemical analysis of biological material
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/28Neurological disorders
    • G01N2800/2814Dementia; Cognitive disorders
    • G01N2800/2821Alzheimer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
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    • G01N2800/2835Movement disorders, e.g. Parkinson, Huntington, Tourette

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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CN201980057467.0A 2018-08-31 2019-08-30 用于治疗神经退行性疾病的对rip激酶的抑制 Pending CN112638405A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862725647P 2018-08-31 2018-08-31
US62/725,647 2018-08-31
PCT/US2019/049071 WO2020047414A1 (en) 2018-08-31 2019-08-30 Inhibition of rip kinases for treating neurodegenerative disorders

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US (2) US20210322427A1 (https=)
EP (1) EP3843773A4 (https=)
JP (1) JP2021535152A (https=)
KR (1) KR20210053303A (https=)
CN (1) CN112638405A (https=)
AU (1) AU2019328532A1 (https=)
CA (1) CA3109364A1 (https=)
WO (1) WO2020047414A1 (https=)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116617224A (zh) * 2023-05-04 2023-08-22 上海交通大学医学院附属瑞金医院 OPN和p38 MAPK信号通路靶向调控剂在制备神经退行性疾病药物中的应用
WO2024099363A1 (zh) * 2022-11-09 2024-05-16 宁波康柏睿格医药科技有限公司 Rip2抑制剂联合免疫检查点抑制剂药物组合物及其应用
CN118304388A (zh) * 2024-04-03 2024-07-09 南通大学 Tak1在制备治疗周围神经损伤药物中的应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022072694A1 (en) * 2020-10-02 2022-04-07 The Trustees Of Dartmouth College Method and agent for treating/preventing neurodegenerative disease and associated neuroinflammation and for evaluating putative prophylactics/therapeutics for treating/preventing neurodegenerative disease and neuroinflammation
US20250122146A1 (en) * 2021-09-30 2025-04-17 The Scripps Research Institute Compounds for reducing neuroinflammation
JP2025519164A (ja) * 2022-05-27 2025-06-24 ジンキュア・コーポレイション 新規なペプチド及びその用途

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US20130005726A1 (en) * 2010-03-08 2013-01-03 Derek Abbott Compositions and methods for treating inflammatory disorders
US20150292012A1 (en) * 2012-10-26 2015-10-15 Case Western Reserve University Biomarkers for nod2 and/or rip2 activity related application
CN105727250A (zh) * 2010-08-23 2016-07-06 康干细胞生物科技有限公司 预防和治疗免疫病变和炎性疾病的包括用nod2激动剂处理的干细胞或其培养物的药物组合物
US20160317518A1 (en) * 2015-04-30 2016-11-03 Samsung Electronics Co., Ltd. Composition for reducing senescence of cell or subject including braf inhibitor and use thereof
US20170003280A1 (en) * 2014-01-11 2017-01-05 The J. David Gladstone Institutes In vitro assays for inhibition of microglial activation
US20180118691A1 (en) * 2014-12-16 2018-05-03 Eudendron S.R.L. Heterocyclic derivatives modulating activity of certain protein kinases

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US20120046329A1 (en) * 2010-08-10 2012-02-23 Sanford-Burnham Medical Research Institute Modulators of nod1 and nod2 signaling, methods of identifying modulators of nod1 and nod2 signaling, and uses thereof
CN105727250A (zh) * 2010-08-23 2016-07-06 康干细胞生物科技有限公司 预防和治疗免疫病变和炎性疾病的包括用nod2激动剂处理的干细胞或其培养物的药物组合物
US20150292012A1 (en) * 2012-10-26 2015-10-15 Case Western Reserve University Biomarkers for nod2 and/or rip2 activity related application
US20170003280A1 (en) * 2014-01-11 2017-01-05 The J. David Gladstone Institutes In vitro assays for inhibition of microglial activation
US20180118691A1 (en) * 2014-12-16 2018-05-03 Eudendron S.R.L. Heterocyclic derivatives modulating activity of certain protein kinases
US20160317518A1 (en) * 2015-04-30 2016-11-03 Samsung Electronics Co., Ltd. Composition for reducing senescence of cell or subject including braf inhibitor and use thereof

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JIALONG CHEN等: "Phosphorylation of Parkin at serine 131 by p38 MAPK promotes mitochondrial dysfunction and neuronal death in mutant A53T α-synuclein model of Parkinson’s disease", CELL DEATH AND DISEASE, 1 June 2018 (2018-06-01), pages 700 *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024099363A1 (zh) * 2022-11-09 2024-05-16 宁波康柏睿格医药科技有限公司 Rip2抑制剂联合免疫检查点抑制剂药物组合物及其应用
CN116617224A (zh) * 2023-05-04 2023-08-22 上海交通大学医学院附属瑞金医院 OPN和p38 MAPK信号通路靶向调控剂在制备神经退行性疾病药物中的应用
CN118304388A (zh) * 2024-04-03 2024-07-09 南通大学 Tak1在制备治疗周围神经损伤药物中的应用

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US20240398824A1 (en) 2024-12-05
CA3109364A1 (en) 2020-03-05
US20210322427A1 (en) 2021-10-21
WO2020047414A1 (en) 2020-03-05
EP3843773A4 (en) 2022-06-08
AU2019328532A1 (en) 2021-03-11
KR20210053303A (ko) 2021-05-11
JP2021535152A (ja) 2021-12-16

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