CR20220062A - Inhibidores de shp2 fosfatasa de tipo pirazolo [3,4-b]pirazina - Google Patents

Inhibidores de shp2 fosfatasa de tipo pirazolo [3,4-b]pirazina

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Publication number
CR20220062A
CR20220062A CR20220062A CR20220062A CR20220062A CR 20220062 A CR20220062 A CR 20220062A CR 20220062 A CR20220062 A CR 20220062A CR 20220062 A CR20220062 A CR 20220062A CR 20220062 A CR20220062 A CR 20220062A
Authority
CR
Costa Rica
Prior art keywords
pyrazolo
pyrazine
phosphatase inhibitors
shp2 phosphatase
compounds
Prior art date
Application number
CR20220062A
Other languages
English (en)
Inventor
Steven Howard
Tadashi Shimamura
John Walter Liebeschuetz
Original Assignee
Taiho Pharmaceutical Co Ltd
Otsuka Pharma Co Ltd
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 Taiho Pharmaceutical Co Ltd, Otsuka Pharma Co Ltd filed Critical Taiho Pharmaceutical Co Ltd
Publication of CR20220062A publication Critical patent/CR20220062A/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • A61K31/4985—Pyrazines or piperazines 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
    • 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
    • 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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biophysics (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La invencion proporciona nuevos derivados de pirazina de formula (I): (I) <img src="data:image/png;base64,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 (***)
CR20220062A 2019-08-20 2020-08-20 Inhibidores de shp2 fosfatasa de tipo pirazolo [3,4-b]pirazina CR20220062A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1911928.8A GB201911928D0 (en) 2019-08-20 2019-08-20 Pharmaceutical compounds
PCT/IB2020/057815 WO2021033153A1 (en) 2019-08-20 2020-08-20 Pyrazolo[3,4-b]pyrazine shp2 phosphatase inhibitors

Publications (1)

Publication Number Publication Date
CR20220062A true CR20220062A (es) 2022-04-20

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CR20220062A CR20220062A (es) 2019-08-20 2020-08-20 Inhibidores de shp2 fosfatasa de tipo pirazolo [3,4-b]pirazina

Country Status (18)

Country Link
US (1) US20230049719A1 (es)
EP (1) EP4017855A1 (es)
JP (1) JP2022546213A (es)
KR (1) KR20220049518A (es)
CN (1) CN114206885A (es)
AU (1) AU2020333251A1 (es)
BR (1) BR112022003184A2 (es)
CA (1) CA3148312A1 (es)
CL (1) CL2022000271A1 (es)
CO (1) CO2022001357A2 (es)
CR (1) CR20220062A (es)
EC (1) ECSP22011086A (es)
GB (1) GB201911928D0 (es)
IL (1) IL289462A (es)
MX (1) MX2022001908A (es)
PE (1) PE20220931A1 (es)
TW (1) TW202124383A (es)
WO (1) WO2021033153A1 (es)

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