WO2019241641A3 - Cancer treatment methods - Google Patents

Cancer treatment methods Download PDF

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Publication number
WO2019241641A3
WO2019241641A3 PCT/US2019/037204 US2019037204W WO2019241641A3 WO 2019241641 A3 WO2019241641 A3 WO 2019241641A3 US 2019037204 W US2019037204 W US 2019037204W WO 2019241641 A3 WO2019241641 A3 WO 2019241641A3
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WO
WIPO (PCT)
Prior art keywords
cancer treatment
treatment methods
methods
tautomer
stereoisomer
Prior art date
Application number
PCT/US2019/037204
Other languages
French (fr)
Other versions
WO2019241641A2 (en
Inventor
Stuart F. J. LE GRICE
David L. Spector
Wenbo XU
Fardokht A. ABULWERDI
Original Assignee
The United States Of America, As Represented By The Secretary, Department Of Health And Human Services
Cold Spring Harbor Laboratory
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Publication date
Application filed by The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, Cold Spring Harbor Laboratory filed Critical The United States Of America, As Represented By The Secretary, Department Of Health And Human Services
Publication of WO2019241641A2 publication Critical patent/WO2019241641A2/en
Publication of WO2019241641A3 publication Critical patent/WO2019241641A3/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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • 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
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Pathology (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed are methods of treating cancer in a patient in need thereof, wherein the cancer has upregulation of MALAT1, comprising administering to the patient an effective amount of a compound of formula (I) or (II), a tautomer thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or any combination thereof: in which R1, R2, R3, R4, R5, X, and m are as described herein. Also provided are methods of inhibiting branching morphogenesis in a tumor organoid cell culture comprising contacting the cell culture with a compound of formula (I) or (II), a tautomer thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or any combination thereof, in which formulas (I), (II), R1, R2, R3, R4, R5, X, and m are as described herein.
PCT/US2019/037204 2018-06-14 2019-06-14 Cancer treatment methods WO2019241641A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862685026P 2018-06-14 2018-06-14
US62/685,026 2018-06-14

Publications (2)

Publication Number Publication Date
WO2019241641A2 WO2019241641A2 (en) 2019-12-19
WO2019241641A3 true WO2019241641A3 (en) 2020-02-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/037204 WO2019241641A2 (en) 2018-06-14 2019-06-14 Cancer treatment methods

Country Status (1)

Country Link
WO (1) WO2019241641A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210012588A (en) * 2019-07-26 2021-02-03 아주대학교산학협력단 Novel Small molecule Compound Inhibiting TLR7 and TLR9 Signaling Pathways and Uses Thereof
CN114504649A (en) * 2022-02-22 2022-05-17 山东大学齐鲁医院 Application of Malat1 inhibitor in prevention and treatment of abdominal aortic aneurysm

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
FARDOKHT A. ABULWERDI ET AL: "Selective Small-Molecule Targeting of a Triple Helix Encoded by the Long Noncoding RNA, MALAT1", ACS CHEMICAL BIOLOGY, vol. 14, no. 2, 8 January 2019 (2019-01-08), pages 223 - 235, XP055622444, ISSN: 1554-8929, DOI: 10.1021/acschembio.8b00807 *
GAYATRI ARUN ET AL: "Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss", GENES AND DEVELOPMENT., vol. 30, no. 1, 23 December 2015 (2015-12-23), US, pages 34 - 51, XP055622098, ISSN: 0890-9369, DOI: 10.1101/gad.270959.115 *
GRYSHCHENKO A A ET AL: "Design, synthesis and biological evaluation of 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones as inhibitors of protein kinase FGFR1", BIOORGANIC & MEDICINAL CHEMISTRY : A TETRAHEDRON PUBLICATION FOR THE RAPID DISSEMINATION OF FULL ORIGINAL RESEARCH PAPERS AND CRITICAL REVIEWS ON BIOMOLECULAR CHEMISTRY, MEDICINAL CHEMISTRY AND RELATED DISCIPLINES, ELSEVIER, NL, vol. 24, no. 9, 21 March 2016 (2016-03-21), pages 2053 - 2059, XP029500711, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2016.03.036 *
KAITLIN J. BASHAM ET AL: "Chemical Genetic Screen Reveals a Role for Desmosomal Adhesion in Mammary Branching Morphogenesis", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 288, no. 4, 25 January 2013 (2013-01-25), US, pages 2261 - 2270, XP055661726, ISSN: 0021-9258, DOI: 10.1074/jbc.M112.411033 *
MASASHI TANIGUCHI ET AL: "Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif", FEBS OPEN BIO, vol. 4, no. 1, 1 January 2014 (2014-01-01), US, pages 328 - 334, XP055622102, ISSN: 2211-5463, DOI: 10.1016/j.fob.2014.03.004 *
SMIRNOVA, T. A. ET AL: "Method for preparation of 1-methyl-5-aryl-2-aminoimidazoles and their reactivity", IZVESTIYA TIMIRYAZEVSKOI SEL'SKOKHOZYAISTVENNOI AKADEMII, no. 4, 2003, pages 132 - 141, XP009516129 *
SUNING CHEN ET AL: "A new ETV6-NTRK3 cell line model reveals MALAT1 as a novel therapeutic target - a short report", CELLULAR ONCOLOGY, vol. 41, no. 1, 8 November 2017 (2017-11-08), Dordrecht, pages 93 - 101, XP055622086, ISSN: 2211-3428, DOI: 10.1007/s13402-017-0356-2 *

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