AR128330A1 - Inductores químicos de degradación conjugados con anticuerpo y métodos de estos - Google Patents

Inductores químicos de degradación conjugados con anticuerpo y métodos de estos

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Publication number
AR128330A1
AR128330A1 ARP230100152A ARP230100152A AR128330A1 AR 128330 A1 AR128330 A1 AR 128330A1 AR P230100152 A ARP230100152 A AR P230100152A AR P230100152 A ARP230100152 A AR P230100152A AR 128330 A1 AR128330 A1 AR 128330A1
Authority
AR
Argentina
Prior art keywords
alkyl
hydrogen
formula
remainder
group
Prior art date
Application number
ARP230100152A
Other languages
English (en)
Inventor
Daniel P Sutherlin
Donglu Zhang
Summer A Baker-Dockrey
Peter S Dragovich
Original Assignee
Genentech Inc
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 Genentech Inc filed Critical Genentech Inc
Publication of AR128330A1 publication Critical patent/AR128330A1/es

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Classifications

    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

El objeto descrito en la presente se refiere en general a moléculas que contienen maleimida hidrolizables que son útiles como ligadores para unir covalentemente inductores químicos de degradación con anticuerpos y con los conjugados producidos con estos, y sus usos para tratar afecciones, y a los usos de los conjugados en el tratamiento de enfermedades y afecciones donde la degradación de la proteína diana es beneficiosa. Reivindicación 1: Un compuesto que tiene la estructura: L¹-D en donde, D es un CIDE; L¹ es un ligador-1 unido covalentemente a D y que tiene una estructura de fórmula (1), en donde, Z es -(CH₂)ₚ- o -CH₂-(CH₂-O-CH₂)ₚ-CH₂-; p es un número entero de 1 a 24; RA es hidrógeno, alquil C₁₋₆ o -(CH₂)ᵛ-arilo, en donde v es 0 o 1; Q se selecciona del grupo que consiste en: i) un resto de fórmula (2), en donde q es 1, 2, 3 o 4; y ii) un resto de fórmula (3), en donde t es 0, 1, 2, 3 o 4; Q¹ es hidrógeno, un resto de fórmula (4) o de fórmula (5), en donde R² es hidrógeno, haloalquil C₁₋₆ o alquil C₁₋₆; y L¹⁻A es: un compuesto de fórmula (6), en donde el resto de fórmula (7) indica el punto de unión a D; w es 0, 1, 2, 3, 4 o 5; J se selecciona del grupo que consiste en alquil C₁₋₅, -N(Rˣ)(Rʸ), -C(O)NH₂, -NH-C(O)-NH₂ y -NH-C(NH)-NH₂, en donde cada uno de Rˣ y Rʸ se selecciona independientemente de hidrógeno y alquil C₁₋₃; K se selecciona del grupo que consiste en alquilen C₁₋₃, -CH(R)-, -C(O)-, -C(O)-O-CH(R)-, -CH₂-O-C(O)-, -CH₂-O-C(O)-NH-CH₂- y -CH₂-O-C(O)-R-[CH₂]ᵘ-O-, en donde R es hidrógeno, alquil C₁₋₃, N(Rˣ)(Rʸ), -O-N(Rˣ)(Rʸ) o C(O)-N(Rˣ)(Rʸ), en donde u es 0, 1, 2 o 3, y en donde cada uno de Rˣ y Rʸ se selecciona independientemente de hidrógeno y alquil C₁₋₃, o Rˣ y Rʸ, junto con el nitrógeno al que está unido cada uno, forman un heterociclilo de 5 a 7 miembros opcionalmente sustituido; cada uno de RC y RD se selecciona independientemente de hidrógeno y alquil C₁₋₃, o RC y RD, junto al carbono al que está unido cada uno, forman un cicloalquil C₃₋₆ opcionalmente sustituido; y cada uno de R⁷ y R⁸ es independientemente hidrógeno, halo, alquil C₁₋₅, alcoxi C₁₋₅ o hidroxilo.
ARP230100152A 2022-01-26 2023-01-24 Inductores químicos de degradación conjugados con anticuerpo y métodos de estos AR128330A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US202263303447P 2022-01-26 2022-01-26

Publications (1)

Publication Number Publication Date
AR128330A1 true AR128330A1 (es) 2024-04-17

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ID=85477901

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP230100152A AR128330A1 (es) 2022-01-26 2023-01-24 Inductores químicos de degradación conjugados con anticuerpo y métodos de estos

Country Status (3)

Country Link
AR (1) AR128330A1 (es)
TW (1) TW202340146A (es)
WO (1) WO2023147328A1 (es)

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TW202340146A (zh) 2023-10-16
WO2023147328A1 (en) 2023-08-03

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