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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Publication of CA3045947A1 publication Critical patent/CA3045947A1/en
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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)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (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

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

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KR20190087622A (ko) 2016-12-08 2019-07-24 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 질환 치료를 위한 이중 류신 지퍼 (dlk) 키나아제의 바이시클로[1.1.1]펜탄 억제제
CN118239937A (zh) 2017-08-09 2024-06-25 戴纳立制药公司 化合物、组合物及方法
DK3676297T3 (da) 2017-09-01 2023-08-14 Denali Therapeutics Inc Forbindelser, sammensætninger og fremgangsmåder
WO2019241244A1 (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
WO2020027723A1 (en) 2018-08-01 2020-02-06 Agency For Science, Technology And Research Bicyclic compounds as kinase modulators, methods and uses thereof
CA3121202A1 (en) 2018-11-30 2020-06-04 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
EP3897670A4 (en) 2018-12-19 2022-09-07 Disarm Therapeutics, Inc. MRSA1 INHIBITORS IN COMBINATION WITH NEUROPROTECTIVE AGENTS
US12091392B2 (en) 2019-02-13 2024-09-17 Denali Therapeutics Inc. Compounds, compositions and methods
MA54953A (fr) 2019-02-13 2021-12-22 Denali Therapeutics Inc Composés, compositions et procédés
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
KR20240055041A (ko) 2021-09-01 2024-04-26 더 유나이티드 스테이츠 오브 아메리카, 애즈 레프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬스 앤드 휴먼 서비시즈 혼합 계통 키나제 억제제 및 억제제의 사용 방법
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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KR20190087622A (ko) 2016-12-08 2019-07-24 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 질환 치료를 위한 이중 류신 지퍼 (dlk) 키나아제의 바이시클로[1.1.1]펜탄 억제제
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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MX2019006645A (es) 2019-08-26
AU2017371084B2 (en) 2022-04-28
AU2017371084A1 (en) 2019-06-20
US20190092764A1 (en) 2019-03-28
BR112019011801A2 (pt) 2019-10-29
ECSP19048477A (es) 2019-07-31
IL267121B (en) 2021-12-01
CO2019006785A2 (es) 2019-07-10
US10093664B2 (en) 2018-10-09
EP3551610A4 (en) 2020-04-22
KR20190087622A (ko) 2019-07-24
MX386838B (es) 2025-03-19
JP7128816B2 (ja) 2022-08-31
JP2020502092A (ja) 2020-01-23
CN110191878B (zh) 2023-05-26
IL267121A (en) 2019-08-29
US20220267311A1 (en) 2022-08-25
EA201991375A1 (ru) 2020-01-20
ES2895257T3 (es) 2022-02-18
US10428057B2 (en) 2019-10-01
EP3551610B1 (en) 2021-08-11
US20180186781A1 (en) 2018-07-05
ZA201904402B (en) 2020-12-23
EP3551610A1 (en) 2019-10-16
CL2019001539A1 (es) 2019-08-23
CN110191878A (zh) 2019-08-30
WO2018107072A1 (en) 2018-06-14

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