ES2914099T3 - Inhibidores novedosos de ULK1 y métodos de uso de los mismos - Google Patents

Inhibidores novedosos de ULK1 y métodos de uso de los mismos Download PDF

Info

Publication number
ES2914099T3
ES2914099T3 ES15836833T ES15836833T ES2914099T3 ES 2914099 T3 ES2914099 T3 ES 2914099T3 ES 15836833 T ES15836833 T ES 15836833T ES 15836833 T ES15836833 T ES 15836833T ES 2914099 T3 ES2914099 T3 ES 2914099T3
Authority
ES
Spain
Prior art keywords
optionally substituted
ulk1
mmol
compound
calc
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES15836833T
Other languages
English (en)
Spanish (es)
Inventor
Reuben J Shaw
Daniel F Egan
Nicholas Cosford
Benjamin Turk
Mitchell Vamos
Dhanya Raveendra Panickar
Matthew Chun
Douglas James Sheffler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yale University
Sanford Burnham Prebys Medical Discovery Institute
Salk Institute for Biological Studies
Original Assignee
Yale University
Sanford Burnham Prebys Medical Discovery Institute
Salk Institute for Biological Studies
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yale University, Sanford Burnham Prebys Medical Discovery Institute, Salk Institute for Biological Studies filed Critical Yale University
Application granted granted Critical
Publication of ES2914099T3 publication Critical patent/ES2914099T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—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
    • A61K31/495—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
    • 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
    • A61K31/535—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
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic 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
    • C07D239/28—Heterocyclic 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
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic 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
    • C07D239/28—Heterocyclic 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
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic 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
    • C07D239/28—Heterocyclic 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic 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
    • C07D239/28—Heterocyclic 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic 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
    • C07D239/28—Heterocyclic 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/12—Heterocyclic 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
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
    • C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/11—Protein-serine/threonine kinases (2.7.11)
    • C12Y207/11001—Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Hematology (AREA)
  • Transplantation (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
ES15836833T 2014-08-25 2015-08-25 Inhibidores novedosos de ULK1 y métodos de uso de los mismos Active ES2914099T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462041559P 2014-08-25 2014-08-25
US201562184212P 2015-06-24 2015-06-24
PCT/US2015/046777 WO2016033100A1 (en) 2014-08-25 2015-08-25 Novel ulk1 inhibitors and methods using same

Publications (1)

Publication Number Publication Date
ES2914099T3 true ES2914099T3 (es) 2022-06-07

Family

ID=55400460

Family Applications (1)

Application Number Title Priority Date Filing Date
ES15836833T Active ES2914099T3 (es) 2014-08-25 2015-08-25 Inhibidores novedosos de ULK1 y métodos de uso de los mismos

Country Status (7)

Country Link
US (4) US10266549B2 (enExample)
EP (2) EP3185868B1 (enExample)
JP (3) JP6684780B2 (enExample)
CA (1) CA2959347C (enExample)
DK (1) DK3185868T3 (enExample)
ES (1) ES2914099T3 (enExample)
WO (1) WO2016033100A1 (enExample)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017156493A1 (en) 2016-03-11 2017-09-14 Denali Therapeutics Inc. Compounds, compositions, and methods
JP6684780B2 (ja) * 2014-08-25 2020-04-22 ソーク インスティテュート フォー バイオロジカル スタディーズ 新規ｕｌｋ１阻害剤およびそれを使用する方法
US11214565B2 (en) 2015-11-20 2022-01-04 Denali Therapeutics Inc. Compound, compositions, and methods
SI3472153T1 (sl) 2016-06-16 2022-01-31 Denali Therapeutics Inc. Pirimidin-2-ilamino-1H-pirazoli kot zaviralci LRRK2 za uporabo pri zdravljenju nevrodegenerativnih motenj
WO2018215801A1 (en) 2017-05-26 2018-11-29 Cancer Research Technology Limited Benzimidazolone derived inhibitors of bcl6
CN111278816B (zh) * 2017-09-04 2024-03-15 C4医药公司 二氢喹啉酮
US10883992B2 (en) * 2018-02-22 2021-01-05 Regents Of The University Of Minnesota Universal kinase substrates and methods of use thereof
SG11202009735QA (en) 2018-04-13 2020-10-29 Cancer Research Tech Ltd Bcl6 inhibitors
CN111362922A (zh) * 2018-12-26 2020-07-03 上海喆邺生物科技有限公司 2,4-二氨基嘧啶衍生物及其用途
CN111362928A (zh) * 2018-12-26 2020-07-03 上海喆邺生物科技有限公司 2,4-二氨基嘧啶衍生物
AU2020274011B2 (en) 2019-05-10 2024-02-15 Deciphera Pharmaceuticals, Llc Heteroarylaminopyrimidine amide autophagy inhibitors and methods of use thereof
RS65019B1 (sr) 2019-05-10 2024-01-31 Deciphera Pharmaceuticals Llc Fenilaminopirimidin amidni inhibitori autofagije i postupci njihove primene
CN119241444A (zh) * 2019-06-17 2025-01-03 德西费拉制药有限责任公司 氨基嘧啶酰胺自噬抑制剂及其使用方法
CN114302878A (zh) 2019-07-03 2022-04-08 大日本住友制药肿瘤公司 酪氨酸激酶非受体1(tnk1)抑制剂及其用途
GB201914860D0 (en) 2019-10-14 2019-11-27 Cancer Research Tech Ltd Inhibitor compounds
CN112824420B (zh) * 2019-11-21 2022-04-26 浙江同源康医药股份有限公司 用作egfr激酶抑制剂的化合物及其应用
WO2021113689A1 (en) * 2019-12-06 2021-06-10 Yale University Spak/osr inhibitors and methods of using same
US20230090742A1 (en) * 2020-01-30 2023-03-23 Sumitomo Pharma Oncology, Inc. Aminopyrimidinylaminobenzonitrile derivatives as nek2 inhibitors
WO2021161648A1 (ja) 2020-02-12 2021-08-19 ユニマテック株式会社 含フッ素ピリミジン化合物およびその製造方法
AU2021218739A1 (en) * 2020-02-14 2022-09-22 Salk Institute For Biological Studies Inhibitors of ULK1/2 and methods of using same
WO2021163627A1 (en) * 2020-02-14 2021-08-19 Salk Institute For Biological Studies Macrocyclic ulk1/2 inhibitors
KR20220154094A (ko) * 2020-02-14 2022-11-21 솔크 인스티튜트 포 바이올로지칼 스터디즈 Ulk1/2 억제제를 이용한 단일 및 병용 요법
EP4126824A1 (en) 2020-03-31 2023-02-08 Theravance Biopharma R&D IP, LLC Substituted pyrimidines and methods of use
CN111484484B (zh) * 2020-04-13 2021-11-23 沈阳药科大学 含芳杂环的2,4-二芳氨基嘧啶衍生物及其制备与应用
CN111732548B (zh) * 2020-06-11 2022-06-17 浙江大学 N2-氨甲酰芳环-2-氨基嘧啶类衍生物及其医药用途
JP7801084B2 (ja) * 2020-09-22 2026-01-16 ベイジーン リミテッド Ｅｇｆｒ阻害剤としてのインドリン化合物及び誘導体
CN116456985A (zh) * 2020-09-23 2023-07-18 深圳市原力生命科学有限公司 作为hpk1调节剂的嘧啶及吡啶衍生物和其使用方法
US20230332243A1 (en) * 2020-09-30 2023-10-19 Salk Institute For Biological Studies Patient selection biomarkers for treatment with ulk inhibitors
CN112920124B (zh) * 2021-01-29 2024-03-01 安徽医科大学 一种嘧啶-2,4-二胺类化合物及其制备方法与应用
WO2023059786A1 (en) * 2021-10-06 2023-04-13 H. Lee Moffitt Cancer Center And Research Institute, Inc. Inhibitors of ulk1 and methods of use
CN117736198A (zh) * 2022-09-21 2024-03-22 科辉智药生物科技(深圳)有限公司 大环含氮冠醚化合物及其作为蛋白激酶抑制剂的应用
WO2024073073A2 (en) * 2022-09-30 2024-04-04 Neuron23, Inc. Kinase modulators and methods of use thereof
WO2024140401A1 (zh) * 2022-12-30 2024-07-04 捷思英达控股有限公司 作为激酶抑制剂的杂环化合物以及包括其的组合物
WO2024233766A1 (en) * 2023-05-10 2024-11-14 Erasca, Inc. Macrocyclic ulk1/2 inhibitors and their use thereof
WO2024249610A2 (en) * 2023-05-30 2024-12-05 The Trustees Of The University Of Pennsylvania Radiolabeled compounds of trimethoprim and uses thereof
WO2025045203A1 (zh) * 2023-09-01 2025-03-06 葆元生物医药科技(杭州)有限公司 杂环化合物及其中间体和应用
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
WO2025117886A1 (en) * 2023-12-01 2025-06-05 Casma Therapeutics, Inc. Ulk complex modulators and uses thereof
WO2025166161A1 (en) * 2024-02-02 2025-08-07 Deciphera Pharmaceuticals, Llc Ulk inhibitors and methods of use thereof
WO2025166180A1 (en) * 2024-02-02 2025-08-07 Deciphera Pharmaceuticals, Llc Ulk inhibitors and methods of use thereof
WO2025166124A1 (en) * 2024-02-02 2025-08-07 Deciphera Pharmaceuticals, Llc Ulk inhibitors and methods of use thereof

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4675189A (en) 1980-11-18 1987-06-23 Syntex (U.S.A.) Inc. Microencapsulation of water soluble active polypeptides
JPS60100516A (ja) 1983-11-04 1985-06-04 Takeda Chem Ind Ltd 徐放型マイクロカプセルの製造法
CA1256638A (en) 1984-07-06 1989-06-27 Motoaki Tanaka Polymer and its production
JP2551756B2 (ja) 1985-05-07 1996-11-06 武田薬品工業株式会社 ポリオキシカルボン酸エステルおよびその製造法
GB0206215D0 (en) * 2002-03-15 2002-05-01 Novartis Ag Organic compounds
UA80767C2 (en) * 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
US7514446B2 (en) * 2003-02-20 2009-04-07 Smithkline Beecham Corporation Pyrimidine compounds
GB0305929D0 (en) * 2003-03-14 2003-04-23 Novartis Ag Organic compounds
US7504396B2 (en) * 2003-06-24 2009-03-17 Amgen Inc. Substituted heterocyclic compounds and methods of use
WO2005049021A1 (en) * 2003-11-03 2005-06-02 Oy Helsinki Transplantation R & D Ltd Materials and methods for inhibiting neointimal hyperplasia
WO2006124874A2 (en) * 2005-05-12 2006-11-23 Kalypsys, Inc. Inhibitors of b-raf kinase
DE102007010801A1 (de) * 2007-03-02 2008-09-04 Bayer Cropscience Ag Diaminopyrimidine als Fungizide
WO2009071535A1 (en) * 2007-12-03 2009-06-11 Boehringer Ingelheim International Gmbh Diaminopyridines for the treatment of diseases which are characterised by excessive or anomal cell proliferation
WO2009083185A2 (en) * 2007-12-28 2009-07-09 Fovea Pharmaceuticals Sa Compositions and methods for prophylaxis and treatment of cellular degenerative ophthalmic disorders
EP2321283B1 (en) 2008-04-16 2016-07-13 Portola Pharmaceuticals, Inc. 2,6-diamino-pyrimidin-5-yl-carboxamides as syk or jak kinases inhibitors
US8338439B2 (en) * 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
US20120114637A1 (en) 2009-05-04 2012-05-10 Santen Pharmaceutical Co., Ltd. Mtor pathway inhibitors for treating ocular disorders
EP2443095A1 (en) * 2009-06-18 2012-04-25 Cellzome Limited Sulfonamides and sulfamides as zap-70 inhibitors
US20130040310A1 (en) * 2009-12-15 2013-02-14 Salk Institute For Biological Studies Ulk1 compositions, inhibitors, screening and methods of use
SG10201500124VA (en) * 2010-01-08 2015-03-30 Agency Science Tech & Res Methods and Compositions for Treating Cancer
WO2011133668A2 (en) * 2010-04-20 2011-10-27 President And Fellows Of Harvard College Methods and compositions for the treatment of cancer
ES2739503T3 (es) 2010-07-09 2020-01-31 Bioverativ Therapeutics Inc Moléculas de cadena simple procesables y polipéptidos producidos usándolas
DE102010034699A1 (de) * 2010-08-18 2012-02-23 Merck Patent Gmbh Pyrimidinderivate
WO2012040602A2 (en) * 2010-09-23 2012-03-29 President And Fellows Of Harvard College Targeting mtor substrates in treating proliferative diseases
WO2012045195A1 (en) * 2010-10-09 2012-04-12 Abbott Laboratories Pyrrolopyrimidines as fak and alk inhibiters for treatment of cancers and other diseases
US8691777B2 (en) 2011-01-27 2014-04-08 Emory University Combination therapy
EP2741784B1 (en) * 2011-03-02 2017-05-17 Board Of Regents, The University Of Texas System Tusc2 therapies
EP2683444A1 (en) * 2011-03-07 2014-01-15 Fondazione Telethon Tfeb phosphorylation inhibitors and uses thereof
AU2012338869A1 (en) 2011-11-15 2014-06-05 Novartis Ag Combination of a phosphoinositide 3-kinase inhibitor and a modulator of the Janus Kinase 2-Signal Transducer and Activator of Transcription 5 pathway
US20130310340A1 (en) 2012-05-16 2013-11-21 Rigel Pharmaceuticals, Inc. Method of treating muscular degradation
US20150250808A1 (en) * 2012-10-15 2015-09-10 Vojo P. Deretic Treatment of autophagy-based disorders and related pharmaceutical compositions, diagnostic and screening assays and kits
IL291945B2 (en) 2012-11-01 2025-11-01 Infinity Pharmaceuticals Inc Treatment of cancers using pi3 kinase isoform modulators
WO2014098932A1 (en) * 2012-12-17 2014-06-26 The Brigham And Women's Hosptial, Inc. Treatment of mtor hyperactive related diseases and disorders
CN103059030B (zh) * 2012-12-28 2015-04-29 北京师范大学 一种具有粘着斑激酶抑制作用的嘧啶类化合物及其制备方法和应用
JP2016506930A (ja) * 2013-01-25 2016-03-07 ライジェル ファーマシューティカルズ， インコーポレイテッド 炎症性腸疾患を処置するための化合物および方法
JP6684780B2 (ja) * 2014-08-25 2020-04-22 ソーク インスティテュート フォー バイオロジカル スタディーズ 新規ｕｌｋ１阻害剤およびそれを使用する方法

Also Published As

Publication number Publication date
US20170342088A1 (en) 2017-11-30
JP6968141B2 (ja) 2021-11-17
US20190152989A1 (en) 2019-05-23
EP3185868A4 (en) 2018-01-10
US20190248806A1 (en) 2019-08-15
US20190284207A1 (en) 2019-09-19
US10689397B2 (en) 2020-06-23
CA2959347C (en) 2023-03-07
US10266549B2 (en) 2019-04-23
CA2959347A1 (en) 2016-03-03
DK3185868T3 (da) 2022-05-23
US10774092B2 (en) 2020-09-15
JP2022017384A (ja) 2022-01-25
JP2020059731A (ja) 2020-04-16
WO2016033100A1 (en) 2016-03-03
JP2017526674A (ja) 2017-09-14
EP3185868A1 (en) 2017-07-05
EP3185868B1 (en) 2022-04-06
EP4070795A1 (en) 2022-10-12
JP6684780B2 (ja) 2020-04-22

Similar Documents

Publication Publication Date Title
ES2914099T3 (es) Inhibidores novedosos de ULK1 y métodos de uso de los mismos
JP6412920B2 (ja) ２−アミノピリド［４，３−Ｄ］ピリミジン−５−オン誘導体及びＷｅｅ−１阻害薬としてのそれらの使用
ES2817700T3 (es) Derivados de 2-(pirimidin-5-il)-tiopirimidina como moduladores de Hsp70 y Hsc70 para el tratamiento de trastornos proliferativos
KR101446742B1 (ko) Ｎ2,ｎ4-비스(4-(피페라진-1-일)페닐)피리미딘-2,4-디아민 유도체 또는 이의 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물
KR102405462B1 (ko) Wee-1 카이네이즈 억제제로 유용한 피리미도피리미디논
AU2014250836C1 (en) Quinazolines and azaquinazolines as dual inhibitors of RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways
JP7244430B2 (ja) Ｗｅｅ－１キナーゼ阻害剤として有用なピリミドピリミジノン
WO2012167415A1 (zh) 嘧啶并嘧啶酮类化合物及其药用组合物和应用
US10961254B2 (en) Pyrimidine compounds and methods using the same
ES2627428T3 (es) Nuevos derivados de 2,3-dihidro-1H-imidazo{1,2-a}pirimidin-5-ona, su preparación y su utilización farmacéutica
WO2018192536A1 (zh) 作为布鲁顿酪氨酸激酶抑制剂的嘧啶并杂环化合物及其应用
WO2015019037A1 (en) Pharmaceutical compounds
WO2014022728A1 (en) Substituted 5 - (quinazolin - 2 - yl) pyrimidin- 2 -amine derivatives useful as pi3k/mtor inhibitors for the treatment of cancer
KR20240044458A (ko) Her2 억제제로서 사용하기 위한 트리시클릭 융합된 피리미딘 화합물
CN103570731B (zh) 嘧啶并三环或嘧啶并四环类化合物及其药用组合物和应用
Nikhar Pyrido-pyrimidinone Derivatives as RIPK2 Kinase and NOD Signaling Inhibitors