CN113260382B - 含整合素配体的细胞抑制性缀合物 - Google Patents

含整合素配体的细胞抑制性缀合物 Download PDF

Info

Publication number
CN113260382B
CN113260382B CN201980087910.9A CN201980087910A CN113260382B CN 113260382 B CN113260382 B CN 113260382B CN 201980087910 A CN201980087910 A CN 201980087910A CN 113260382 B CN113260382 B CN 113260382B
Authority
CN
China
Prior art keywords
tumor
cancer
acid
compound
compounds
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201980087910.9A
Other languages
English (en)
Chinese (zh)
Other versions
CN113260382A (zh
Inventor
H-G·勒珍
B·斯特尔特-路德维格
C·C·科皮茨
约尔格·克尔德尼希
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Bayer Pharma AG
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 Bayer Pharma AG filed Critical Bayer Pharma AG
Publication of CN113260382A publication Critical patent/CN113260382A/zh
Application granted granted Critical
Publication of CN113260382B publication Critical patent/CN113260382B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • 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
    • A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • 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
    • C07D491/22—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 four or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
CN201980087910.9A 2018-11-05 2019-10-30 含整合素配体的细胞抑制性缀合物 Active CN113260382B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP18204423.0 2018-11-05
EP18204423 2018-11-05
PCT/EP2019/079601 WO2020094471A1 (en) 2018-11-05 2019-10-30 Cytostatic conjugates with integrin ligands

Publications (2)

Publication Number Publication Date
CN113260382A CN113260382A (zh) 2021-08-13
CN113260382B true CN113260382B (zh) 2024-09-13

Family

ID=64453279

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980087910.9A Active CN113260382B (zh) 2018-11-05 2019-10-30 含整合素配体的细胞抑制性缀合物

Country Status (16)

Country Link
US (2) US20210386864A1 (https=)
EP (1) EP3876993A1 (https=)
JP (1) JP7509768B2 (https=)
KR (1) KR20210100607A (https=)
CN (1) CN113260382B (https=)
AR (1) AR116999A1 (https=)
AU (1) AU2019376293A1 (https=)
BR (1) BR112021008232A2 (https=)
CA (1) CA3118041A1 (https=)
CL (1) CL2021001142A1 (https=)
EA (1) EA202191244A1 (https=)
IL (1) IL282748B2 (https=)
MX (1) MX2021005134A (https=)
SG (1) SG11202104491SA (https=)
TW (1) TW202039005A (https=)
WO (1) WO2020094471A1 (https=)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3313523A2 (en) 2015-06-23 2018-05-02 Bayer Pharma Aktiengesellschaft Targeted conjugates of ksp inhibitors
EP3919518A1 (en) 2016-06-15 2021-12-08 Bayer Pharma Aktiengesellschaft Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies
CN110312534B (zh) 2016-12-21 2023-04-04 拜耳制药股份公司 具有酶促可裂解基团的抗体-药物-缀合物(adc)
US12059472B2 (en) 2016-12-21 2024-08-13 Bayer Aktiengesellschaft Prodrugs of cytotoxic active agents having enzymatically cleavable groups
CN110072556B (zh) 2016-12-21 2023-05-02 拜耳制药股份公司 具有ksp抑制剂的特异性抗体药物缀合物(adc)
EA202191244A1 (ru) * 2018-11-05 2021-10-11 Байер Фарма Акциенгезельшафт Новые цитостатические конъюгаты с лигандами интегрина
WO2023057814A1 (en) 2021-10-04 2023-04-13 Vincerx Pharma Gmbh Compounds, pharmaceutical compositions, and methods for the treatment, prevention, or management of hyperproliferative disorders
WO2023057813A1 (en) 2021-10-04 2023-04-13 Vincerx Pharma Gmbh Compounds, pharmaceutical compositions, and methods for the treatment, prevention, or management of hyperproliferative disorders
WO2023057812A1 (en) 2021-10-04 2023-04-13 Vincerx Pharma Gmbh Compounds, pharmaceutical compositions, and methods for the treatment, prevention, or management of hyperproliferative disorder
JP2025537882A (ja) 2022-11-17 2025-11-20 ハンス－ゲオルク レルケン 腫瘍微小環境において切断可能な小分子－薬物コンジュゲート
WO2024105206A1 (en) 2022-11-17 2024-05-23 Vincerx Pharma Gmbh Antibody-drug-conjugates cleavable in a tumor microenvironment
US20240376212A1 (en) * 2023-04-25 2024-11-14 Targetthera Llc Alpha v-integrin targeted small molecule drug conjugates
CN119143798B (zh) * 2024-08-01 2025-09-30 河北医科大学 一种骨靶向阿仑膦酸-普萘洛尔及其制备方法与应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1238678A1 (en) * 2001-03-08 2002-09-11 Bayer Aktiengesellschaft Enzyme-activated cytostatic conjugates with integrin ligands
JP2011523415A (ja) * 2008-05-20 2011-08-11 シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ 新規な二重標的化抗腫瘍複合体

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8705477D0 (en) 1987-03-09 1987-04-15 Carlton Med Prod Drug delivery systems
US4975278A (en) 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US4943579A (en) 1987-10-06 1990-07-24 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Water soluble prodrugs of camptothecin
FR2676058B1 (fr) 1991-04-30 1994-02-25 Hoechst Lab Prodrogues glycosylees, leur procede de preparation et leur utilisation dans le traitement des cancers.
DE4229903A1 (de) 1992-09-08 1994-03-10 Bayer Ag Neue Acetale von Ketophosphamid und Alkylglycosiden
DE4236237A1 (de) 1992-10-27 1994-04-28 Behringwerke Ag Prodrugs, ihre Herstellung und Verwendung als Arzneimittel
US5646159A (en) 1994-07-20 1997-07-08 Research Triangle Institute Water-soluble esters of camptothecin compounds
CA2265484C (en) 1996-09-10 2008-12-02 The Burnham Institute Tumor homing molecules, conjugates derived therefrom, and methods of using same
CA2370245A1 (en) 1999-05-14 2000-11-23 Boehringer Ingelheim Pharmaceuticals, Inc. Enzyme-activated anti-tumor prodrug compounds
EA202191244A1 (ru) * 2018-11-05 2021-10-11 Байер Фарма Акциенгезельшафт Новые цитостатические конъюгаты с лигандами интегрина

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1238678A1 (en) * 2001-03-08 2002-09-11 Bayer Aktiengesellschaft Enzyme-activated cytostatic conjugates with integrin ligands
JP2011523415A (ja) * 2008-05-20 2011-08-11 シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ 新規な二重標的化抗腫瘍複合体

Also Published As

Publication number Publication date
US20240325553A1 (en) 2024-10-03
JP2022506299A (ja) 2022-01-17
TW202039005A (zh) 2020-11-01
BR112021008232A2 (pt) 2021-08-03
JP7509768B2 (ja) 2024-07-02
IL282748B2 (en) 2025-07-01
CA3118041A1 (en) 2020-05-14
CL2021001142A1 (es) 2021-11-12
AR116999A1 (es) 2021-06-30
IL282748A (en) 2021-06-30
IL282748B1 (en) 2025-03-01
WO2020094471A1 (en) 2020-05-14
US20210386864A1 (en) 2021-12-16
MX2021005134A (es) 2021-07-07
CN113260382A (zh) 2021-08-13
EP3876993A1 (en) 2021-09-15
AU2019376293A1 (en) 2021-06-03
SG11202104491SA (en) 2021-05-28
KR20210100607A (ko) 2021-08-17
EA202191244A1 (ru) 2021-10-11

Similar Documents

Publication Publication Date Title
CN113260382B (zh) 含整合素配体的细胞抑制性缀合物
JP2022506299A5 (https=)
ES2910941T3 (es) Ligandos de proteína de activación de fibroblastos para aplicaciones de administración dirigida
JP7191938B2 (ja) Ｉｇｆ－１ｒモノクローナル抗体及びその使用
ES2981364T3 (es) Compuestos para liberación clic rápida y eficiente
JP5791707B2 (ja) 新規アウリスタチン誘導体およびその使用
AU2022246407B2 (en) Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
AU2018368520B2 (en) Ligand-drug-conjugates as substrates for selective cleavage by the exopeptidase activity of Cathepsin B
CA3171025A1 (en) Fibroblast activation protein ligands for targeted delivery applications
CN120393061A (zh) 放射性免疫缀合物与dna损伤和修复抑制剂组合疗法
CA3210473A1 (en) Branched linkers for antibody-drug conjugates and methods of use thereof
TW202330539A (zh) 用於治療、預防或管理過度增生性病症之化合物、醫藥組合物及方法
CN117430660A (zh) 奥瑞他汀f类似物及其抗体药物偶联物与应用
CN120390747A (zh) 用于靶向递送应用的碳酸酐酶ix配体
HK40049734A (en) Cytostatic conjugates with integrin ligands
JP2024536627A (ja) 過剰増殖性障害の処置、予防、または管理のための化合物、医薬組成物、および方法
HK40049734B (zh) 含整合素配体的细胞抑制性缀合物
TW202337500A (zh) 抗體結合的化學降解誘導物及其方法
EA046139B1 (ru) Конъюгаты лиганда-лекарственного средства в качестве субстратов для селективного расщепления под действием экзопептидазной активности катепсина b
HK1184363B (en) Novel auristatin derivatives and use thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40049734

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant