CA3045947A1 - Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease - Google Patents

Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease Download PDF

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Publication number
CA3045947A1
CA3045947A1 CA3045947A CA3045947A CA3045947A1 CA 3045947 A1 CA3045947 A1 CA 3045947A1 CA 3045947 A CA3045947 A CA 3045947A CA 3045947 A CA3045947 A CA 3045947A CA 3045947 A1 CA3045947 A1 CA 3045947A1
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Prior art keywords
compound
4alkyl
disease
mmol
recited
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Pending
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CA3045947A
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English (en)
French (fr)
Inventor
Michael J. Soth
Gang Liu
Kang Le
Jason Cross
Philip Jones
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University of Texas System
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University of Texas System
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    • 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
    • A61K31/4439—Non 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
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further 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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (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)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA3045947A 2016-12-08 2017-12-08 Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease Pending CA3045947A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662431504P 2016-12-08 2016-12-08
US62/431,504 2016-12-08
PCT/US2017/065385 WO2018107072A1 (en) 2016-12-08 2017-12-08 Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease

Publications (1)

Publication Number Publication Date
CA3045947A1 true CA3045947A1 (en) 2018-06-14

Family

ID=62492159

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3045947A Pending CA3045947A1 (en) 2016-12-08 2017-12-08 Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease

Country Status (17)

Country Link
US (3) US10093664B2 (enExample)
EP (1) EP3551610B1 (enExample)
JP (1) JP7128816B2 (enExample)
KR (1) KR20190087622A (enExample)
CN (1) CN110191878B (enExample)
AU (1) AU2017371084B2 (enExample)
BR (1) BR112019011801A2 (enExample)
CA (1) CA3045947A1 (enExample)
CL (1) CL2019001539A1 (enExample)
CO (1) CO2019006785A2 (enExample)
EA (1) EA201991375A1 (enExample)
EC (1) ECSP19048477A (enExample)
ES (1) ES2895257T3 (enExample)
IL (1) IL267121B (enExample)
MX (1) MX386838B (enExample)
WO (1) WO2018107072A1 (enExample)
ZA (1) ZA201904402B (enExample)

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BR112019011801A2 (pt) 2016-12-08 2019-10-29 Univ Texas composto, composição farmacêutica e método de inibição de dlk, método de tratamento de uma doença mediada por dlk, método de tratamento de câncer e redução do desenvolvimento de um distúrbio neurológico induzido por quimioterapia e método para alcançar um efeito em um paciente
CR20200054A (es) 2017-08-09 2020-03-21 Denali Therapeutics Inc Compuestos, composiciones y métodos
HUE062446T2 (hu) 2017-09-01 2023-11-28 Denali Therapeutics Inc Vegyületek, készítmények és eljárások
US20190382396A1 (en) * 2018-06-13 2019-12-19 Board Of Regents, The University Of Texas System Salts of bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease
GB201811165D0 (en) * 2018-07-06 2018-08-29 Metrion Biosciences Ltd Novel compounds
SG11202101060WA (en) * 2018-08-01 2021-02-25 Agency Science Tech & Res Bicyclic compounds as kinase modulators, methods and uses thereof
EP3886854A4 (en) 2018-11-30 2022-07-06 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
CN113164508B (zh) 2018-12-19 2025-07-08 达萨玛治疗公司 与神经保护剂组合的sarm1抑制剂
MA54959A (fr) 2019-02-13 2021-12-22 Denali Therapeutics Inc Composés, compositions et procédés
EP3923935A4 (en) 2019-02-13 2022-10-26 Denali Therapeutics Inc. COMPOUNDS, COMPOSITIONS AND METHODS
IL291665B2 (en) * 2019-09-27 2025-07-01 Univ Texas Inhibitors of receptor interacting protein kinase i for the treatment of disease
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
CA3193736A1 (en) * 2020-09-02 2022-03-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lzk-targeting degraders and methods of use
CA3229861A1 (en) * 2021-09-01 2023-03-09 John F. BROGNARD Mixed lineage kinase inhibitors and methods of use
CN115974795A (zh) * 2022-12-26 2023-04-18 杭州师范大学 一种含全氟烷基和n杂环二取代双环[1.1.1]戊烷及其合成方法
WO2025021997A1 (en) 2023-07-27 2025-01-30 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts New map4k1 inhibitors

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JP2006524702A (ja) 2003-04-25 2006-11-02 カイロン コーポレイション ピリジル置換ケトライド抗体
TW200944520A (en) 2008-01-29 2009-11-01 Glaxo Group Ltd Spiro compounds as NPY Y5 receptor antagonists
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MX2015009270A (es) * 2013-01-18 2015-10-30 Hoffmann La Roche Pirazoles sustituidos en posicion 3 y uso de los mismos como inhibidores de la cinasa cremallera de leucinas dual (dlk).
CN104119340A (zh) 2013-01-22 2014-10-29 韩冰 一类蛋白酶抑制剂及其制备方法和用途
PE20161063A1 (es) 2013-05-01 2016-10-22 Hoffmann La Roche Compuestos de biheteroarilo y usos de los mismos
WO2014177524A1 (en) 2013-05-01 2014-11-06 F. Hoffmann-La Roche Ag C-linked heterocycloalkyl substituted pyrimidines and their uses
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.
CN113336653A (zh) * 2014-03-07 2021-09-03 里科瑞尔姆Ip控股有限责任公司 螺桨烷衍生物及合成
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PE20171789A1 (es) * 2015-03-02 2017-12-28 Bristol Myers Squibb Co Inhibidores del factor beta de crecimiento de transformacion (tgf-beta)
ES2788160T3 (es) * 2015-04-03 2020-10-20 Recurium Ip Holdings Llc Compuestos espirocíclicos
BR112019004243A2 (pt) 2016-08-29 2019-06-04 Univ Texas composto, composição farmacêutica, método para inibição de quinase do zíper de leucina dupla, método para tratamento de uma doença mediada por quinase do zíper de leucina dupla e método para obter um efeito em um paciente
BR112019011801A2 (pt) 2016-12-08 2019-10-29 Univ Texas composto, composição farmacêutica e método de inibição de dlk, método de tratamento de uma doença mediada por dlk, método de tratamento de câncer e redução do desenvolvimento de um distúrbio neurológico induzido por quimioterapia e método para alcançar um efeito em um paciente
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

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JP7128816B2 (ja) 2022-08-31
ES2895257T3 (es) 2022-02-18
BR112019011801A2 (pt) 2019-10-29
EP3551610A1 (en) 2019-10-16
US10093664B2 (en) 2018-10-09
EA201991375A1 (ru) 2020-01-20
EP3551610A4 (en) 2020-04-22
AU2017371084A1 (en) 2019-06-20
MX2019006645A (es) 2019-08-26
CN110191878A (zh) 2019-08-30
MX386838B (es) 2025-03-19
CL2019001539A1 (es) 2019-08-23
ZA201904402B (en) 2020-12-23
JP2020502092A (ja) 2020-01-23
US20190092764A1 (en) 2019-03-28
US10428057B2 (en) 2019-10-01
CN110191878B (zh) 2023-05-26
IL267121B (en) 2021-12-01
US20220267311A1 (en) 2022-08-25
AU2017371084B2 (en) 2022-04-28
KR20190087622A (ko) 2019-07-24
WO2018107072A1 (en) 2018-06-14
IL267121A (en) 2019-08-29
US20180186781A1 (en) 2018-07-05
ECSP19048477A (es) 2019-07-31
CO2019006785A2 (es) 2019-07-10
EP3551610B1 (en) 2021-08-11

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