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PE20211388A1 - Compuestos - Google Patents

Compuestos

Info

Publication number
PE20211388A1
PE20211388A1 PE2020002105A PE2020002105A PE20211388A1 PE 20211388 A1 PE20211388 A1 PE 20211388A1 PE 2020002105 A PE2020002105 A PE 2020002105A PE 2020002105 A PE2020002105 A PE 2020002105A PE 20211388 A1 PE20211388 A1 PE 20211388A1
Authority
PE
Peru
Prior art keywords
halogen
alkyl
alkoxy
compounds
isoindolin
Prior art date
Application number
PE2020002105A
Other languages
English (en)
Inventor
Martin Duplessis
Annick Goergler
Georg Jaeschke
Buelent Kocer
Bernd Kuhn
Kiel Lazarski
Yanke Liang
Yvonne Alice Nagel
Sander Ulrike Obst
Antonio Ricci
Daniel Rueher
Sandra Steiner
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of PE20211388A1 publication Critical patent/PE20211388A1/es

Links

Classifications

    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems
    • 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
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K47/02—Inorganic 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
    • A61K47/06—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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • 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
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Botany (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente invencion proporciona compuestos de Formula I, en donde: L esta ausente o es C?C; A es como se indica; B es arilo o heteroarilo; C es heteroarilo; R2 es halogeno, alquilo opcionalmente sustituido, entre otras opciones; R3 es amino, alquilo, alcoxi, CN, halogeno, entre otras opciones; R7 es H, halogeno, halogeno-alcoxi, alcoxi, alquilo; R8 es H, halogeno, alcoxi, alquilo; R9 es H, halogeno, halogeno-alcoxi, alcoxi, alquilo; m es 0, 1, 2; p es 0, 1. Entre los compuestos preferidos tenemos los siguientes: (2RS)-2-(6,7-dihidro-5H-pirrolizin-1-il)-2-[4-fluoro-6-[2-[4-[(4-hidroxi-1-piperidil)metil]fenil]etinil]-1-oxo-isoindolin-2-il]-N-tiazol-2-il-acetamida; (2RS)-2-[4-cloro-6-[4-(4-etilpiperazin-1-il)fenil]-1-oxo-isoindolin-2-il]-2-(6,7-dihidro-5Hpirrolo[1,2-c]imidazol-1-il)-N-tiazol-2-il-acetamida; entre otros. Estos compuestos son inhibidores alostericos selectivos de mutantes de EGFR que contienen T790M/L858R, T790M/L858R/C797S, L858R, L858R/C797S, y son utiles para el tratamiento terapeutico y/o profilactico del cancer.
PE2020002105A 2018-06-29 2019-06-27 Compuestos PE20211388A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18180758 2018-06-29
PCT/EP2019/067111 WO2020002487A1 (en) 2018-06-29 2019-06-27 Compounds

Publications (1)

Publication Number Publication Date
PE20211388A1 true PE20211388A1 (es) 2021-07-27

Family

ID=62837714

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2020002105A PE20211388A1 (es) 2018-06-29 2019-06-27 Compuestos

Country Status (20)

Country Link
US (1) US12209091B2 (es)
EP (1) EP3814351A1 (es)
JP (1) JP7411588B2 (es)
KR (1) KR20210025535A (es)
CN (1) CN112437774A (es)
AR (1) AR115663A1 (es)
AU (1) AU2019294414B2 (es)
BR (1) BR112020026450A2 (es)
CA (1) CA3103166A1 (es)
CL (1) CL2020003354A1 (es)
CR (1) CR20200625A (es)
IL (1) IL279800B2 (es)
MA (1) MA53003A (es)
MX (1) MX2020014085A (es)
PE (1) PE20211388A1 (es)
PH (1) PH12020552154A1 (es)
SG (1) SG11202011818YA (es)
TW (1) TWI833773B (es)
WO (1) WO2020002487A1 (es)
ZA (1) ZA202007956B (es)

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JP2021527437A (ja) 2018-06-22 2021-10-14 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｓｃｎ９ａ発現を調節するためのオリゴヌクレオチド
JP7530390B2 (ja) * 2019-06-21 2024-08-07 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 新規ｅｇｆｒ阻害剤
LT3986897T (lt) * 2019-06-21 2023-11-10 F. Hoffmann-La Roche Ag Egfr inhibitorius, skirtas vėžiui gydyti
JOP20220107A1 (ar) 2019-11-11 2023-01-30 Dana Farber Cancer Inst Inc مثبطات egfr تفارغية وطرق استخدامها
AR120799A1 (es) * 2019-12-20 2022-03-16 Hoffmann La Roche 2-[4-cloro-6-[2-[4-[[4-(hidroximetil)-1-piperidil]metil]fenil]etinil]-1-oxoisoindolin-2-il]-2-(6,7-dihidro-5h-pirrolo[1,2-c]imidazol-1-il)-n-tiazol-2-il-acetamida como inhibidor de egfr
CN114901277B (zh) 2019-12-20 2024-05-17 C4医药公司 用于egfr降解的异吲哚啉酮和吲唑化合物
EP4161516A4 (en) * 2020-06-09 2024-08-07 Dana-Farber Cancer Institute, Inc. ALLOSTERIC EGFR INHIBITORS AND METHODS OF USE THEREOF
EP4255906A1 (en) * 2020-12-01 2023-10-11 F. Hoffmann-La Roche AG New indazole derivatives
PE20240099A1 (es) * 2020-12-01 2024-01-18 Hoffmann La Roche Nuevos derivados de indazol acetileno
EP4255907A1 (en) * 2020-12-01 2023-10-11 F. Hoffmann-La Roche AG New indazole derivatives
AU2022280070A1 (en) * 2021-05-26 2023-11-16 C4 Therapeutics, Inc. Egfr degraders to treat cancer metastasis to the brain or cns
WO2023283130A1 (en) 2021-07-04 2023-01-12 Newave Pharmaceutical Inc. Isoquinoline derivatives as mutant egfr modulators and uses thereof
CN118317784A (zh) 2021-09-30 2024-07-09 江苏恒瑞医药股份有限公司 吡咯并苯并二氮杂卓类衍生物及其偶联物、其制备方法及其应用
KR20250130345A (ko) * 2023-01-11 2025-09-01 다나-파버 캔서 인스티튜트 인크. 돌연변이체 선택적 egfr 저해제

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MX2017014550A (es) 2015-05-14 2018-02-26 Wistar Inst Inhibidores del antigeno nuclear epstein-barr 1 (ebna1) y metodos que los utilizan.
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Also Published As

Publication number Publication date
EP3814351A1 (en) 2021-05-05
IL279800A (en) 2021-03-01
IL279800B2 (en) 2024-02-01
CA3103166A1 (en) 2020-01-02
TW202019930A (zh) 2020-06-01
AR115663A1 (es) 2021-02-10
KR20210025535A (ko) 2021-03-09
AU2019294414A1 (en) 2020-12-24
ZA202007956B (en) 2021-10-27
MA53003A (fr) 2021-05-05
AU2019294414B2 (en) 2023-06-29
JP7411588B2 (ja) 2024-01-11
US12209091B2 (en) 2025-01-28
TWI833773B (zh) 2024-03-01
CL2020003354A1 (es) 2021-07-19
SG11202011818YA (en) 2020-12-30
CR20200625A (es) 2021-02-05
CN112437774A (zh) 2021-03-02
PH12020552154A1 (en) 2021-07-05
US20210079005A1 (en) 2021-03-18
MX2020014085A (es) 2021-03-09
IL279800B1 (en) 2023-10-01
WO2020002487A1 (en) 2020-01-02
BR112020026450A2 (pt) 2021-03-23
JP2021529775A (ja) 2021-11-04

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