TWI870468B - 治療性共軛物 - Google Patents

治療性共軛物 Download PDF

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Publication number
TWI870468B
TWI870468B TW109132462A TW109132462A TWI870468B TW I870468 B TWI870468 B TW I870468B TW 109132462 A TW109132462 A TW 109132462A TW 109132462 A TW109132462 A TW 109132462A TW I870468 B TWI870468 B TW I870468B
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TW
Taiwan
Prior art keywords
group
compound
alkyl
pharmaceutically acceptable
optionally substituted
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TW109132462A
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English (en)
Chinese (zh)
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TW202126307A (zh
Inventor
尼爾 達汪
詹姆士 布萊爾
羅伯特 波尼
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美商托特斯藥品公司
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Publication of TW202126307A publication Critical patent/TW202126307A/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
TW109132462A 2019-09-19 2020-09-18 治療性共軛物 TWI870468B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201962902554P 2019-09-19 2019-09-19
US62/902,554 2019-09-19
US202063078055P 2020-09-14 2020-09-14
US63/078,055 2020-09-14

Publications (2)

Publication Number Publication Date
TW202126307A TW202126307A (zh) 2021-07-16
TWI870468B true TWI870468B (zh) 2025-01-21

Family

ID=74883745

Family Applications (1)

Application Number Title Priority Date Filing Date
TW109132462A TWI870468B (zh) 2019-09-19 2020-09-18 治療性共軛物

Country Status (19)

Country Link
US (4) US20220387603A1 (https=)
EP (1) EP4031143B1 (https=)
JP (1) JP7810640B2 (https=)
KR (1) KR20220079866A (https=)
CN (2) CN120789282A (https=)
AU (1) AU2020349543A1 (https=)
BR (1) BR112022005026A2 (https=)
CA (1) CA3154079A1 (https=)
CL (1) CL2022000665A1 (https=)
CO (1) CO2022003703A2 (https=)
DK (1) DK4031143T3 (https=)
ES (1) ES3043134T3 (https=)
IL (1) IL291486B1 (https=)
MX (1) MX2022003217A (https=)
PE (1) PE20230091A1 (https=)
PH (1) PH12022550494A1 (https=)
TW (1) TWI870468B (https=)
WO (1) WO2021055747A1 (https=)
ZA (1) ZA202203201B (https=)

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KR20220079866A (ko) 2019-09-19 2022-06-14 토투스 메디신스 아이엔씨. 치료 접합체
WO2022198024A1 (en) * 2021-03-18 2022-09-22 Totus Medicines Inc. Therapeutic conjugates
WO2023183936A2 (en) * 2022-03-24 2023-09-28 Totus Medicines Inc. Combination therapy of a pi3k inhibitor and kras inhibitor and methods of use thereof
AU2023240100A1 (en) 2022-03-24 2024-10-03 Totus Medicines Inc. Crystalline forms and salts of a pi3k inhibitor and methods of making and methods of use thereof
AU2023249795A1 (en) 2022-04-08 2024-10-17 Shy Therapeutics, Llc Compounds that interact with ras superfamily proteins for treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
WO2024086664A2 (en) * 2022-10-18 2024-04-25 Totus Medicines Inc. Covalent inhibitors of wild-type and mutant pi3k and method of uses thereof
WO2024220380A2 (en) * 2023-04-16 2024-10-24 Totus Medicines Inc. Pi3k assays and probe compounds therein
EP4704841A1 (en) 2023-05-05 2026-03-11 Eli Lilly and Company Imlunestrant or salts thereof for use in treating and preventing central nervous system (cns) metastases in subjects having er+ breast cancer
CN117126164B (zh) * 2023-08-30 2024-09-27 山东轩硕医药科技有限公司 一种吡咯并三嗪类化合物，其制备方法及用途
WO2025072796A1 (en) * 2023-09-27 2025-04-03 Totus Medicines Inc. Pharmaceutical compositions and methods of use thereof

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Also Published As

Publication number Publication date
CN120789282A (zh) 2025-10-17
CA3154079A1 (en) 2021-03-25
CN114599366B (zh) 2025-05-09
JP2022548135A (ja) 2022-11-16
US20240366771A1 (en) 2024-11-07
US20220211855A1 (en) 2022-07-07
US20230096658A1 (en) 2023-03-30
MX2022003217A (es) 2022-06-29
IL291486A (en) 2022-05-01
US12029791B2 (en) 2024-07-09
KR20220079866A (ko) 2022-06-14
CL2022000665A1 (es) 2022-10-28
ES3043134T3 (en) 2025-11-24
EP4031143A4 (en) 2023-11-01
CO2022003703A2 (es) 2022-07-08
IL291486B1 (en) 2026-03-01
US11484597B2 (en) 2022-11-01
AU2020349543A1 (en) 2022-03-24
EP4031143A1 (en) 2022-07-27
EP4031143B1 (en) 2025-07-30
DK4031143T3 (da) 2025-10-13
JP7810640B2 (ja) 2026-02-03
WO2021055747A1 (en) 2021-03-25
PE20230091A1 (es) 2023-01-16
US20220387603A1 (en) 2022-12-08
BR112022005026A2 (pt) 2022-06-21
CN114599366A (zh) 2022-06-07
PH12022550494A1 (en) 2023-02-27
TW202126307A (zh) 2021-07-16
ZA202203201B (en) 2023-11-29

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