[go: up one dir, main page]

BRPI1008749B8 - compostos derivados de benzodiazepina, seus conjugados, composição farmacêutica, seu uso e seus processos de preparação - Google Patents

compostos derivados de benzodiazepina, seus conjugados, composição farmacêutica, seu uso e seus processos de preparação

Info

Publication number
BRPI1008749B8
BRPI1008749B8 BRPI1008749A BRPI1008749A BRPI1008749B8 BR PI1008749 B8 BRPI1008749 B8 BR PI1008749B8 BR PI1008749 A BRPI1008749 A BR PI1008749A BR PI1008749 A BRPI1008749 A BR PI1008749A BR PI1008749 B8 BRPI1008749 B8 BR PI1008749B8
Authority
BR
Brazil
Prior art keywords
conjugates
heterocyclic ring
compounds
pharmaceutical composition
ring
Prior art date
Application number
BRPI1008749A
Other languages
English (en)
Inventor
Louis Miller Michael
Elliott Fishkin Nathan
V J Chari Ravi
Yongxin Zhao Robert
Li Wei
Original Assignee
Immunogen 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 Immunogen Inc filed Critical Immunogen Inc
Publication of BRPI1008749A2 publication Critical patent/BRPI1008749A2/pt
Publication of BRPI1008749B1 publication Critical patent/BRPI1008749B1/pt
Publication of BRPI1008749B8 publication Critical patent/BRPI1008749B8/pt

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • 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
    • A61K47/50—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
    • A61K47/68—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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6863—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
    • 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
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
    • 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
    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • 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
    • C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

derivados de benzodiazepina. a presente invenção refere-se a novos derivados de benzodiazepina com atividade antiproliferativa e, mais especificamente, a novas benzodiazepinas de fórmula (i) e (ii), nas quais o anel diazepina (b) é fundido com um anel heterocíclico (cd), em que o anel heterocíclico é bicíclico ou um composto de fórmula (iii), no qual o anel diazepina (b) é fundido com um anel heterocíclico (c), em que o anel heterocíclico é monocíclico. a invenção fornece dímeros citotóxicos destes compostos. a invenção também fornece conjugados dos monômeros e dos dímeros. a invenção ainda fornece composições e métodos úteis para inibir crescimento celular anormal ou tratar um distúrbio proliferativo em um mamífero usando os compostos ou conjugados da invenção. a invenção ainda se refere a métodos para usar os compostos ou conjugados para diagnósticos in vitro, in situ e in vivo ou tratamento de células de mamífero ou condições patológicas associadas.
BRPI1008749A 2009-02-05 2010-02-04 compostos derivados de benzodiazepina, seus conjugados, composição farmacêutica, seu uso e seus processos de preparação BRPI1008749B8 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US15020109P 2009-02-05 2009-02-05
US61/150,201 2009-02-05
PCT/US2010/023150 WO2010091150A1 (en) 2009-02-05 2010-02-04 Novel benzodiazepine derivatives

Publications (3)

Publication Number Publication Date
BRPI1008749A2 BRPI1008749A2 (pt) 2015-08-25
BRPI1008749B1 BRPI1008749B1 (pt) 2020-12-22
BRPI1008749B8 true BRPI1008749B8 (pt) 2021-05-25

Family

ID=42540587

Family Applications (1)

Application Number Title Priority Date Filing Date
BRPI1008749A BRPI1008749B8 (pt) 2009-02-05 2010-02-04 compostos derivados de benzodiazepina, seus conjugados, composição farmacêutica, seu uso e seus processos de preparação

Country Status (16)

Country Link
US (10) US8426402B2 (pt)
EP (3) EP3360879A1 (pt)
JP (4) JP5977522B2 (pt)
KR (3) KR101835033B1 (pt)
CN (4) CN108727407B (pt)
AU (1) AU2010210646B2 (pt)
BR (1) BRPI1008749B8 (pt)
CA (2) CA3014224C (pt)
ES (1) ES2604668T3 (pt)
IL (6) IL271761B (pt)
MX (2) MX2011008328A (pt)
NZ (2) NZ594177A (pt)
RU (2) RU2683325C2 (pt)
SG (3) SG173152A1 (pt)
WO (1) WO2010091150A1 (pt)
ZA (1) ZA201105352B (pt)

Families Citing this family (190)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100056762A1 (en) 2001-05-11 2010-03-04 Old Lloyd J Specific binding proteins and uses thereof
PT1392359E (pt) 2001-05-11 2010-01-27 Ludwig Inst For Cancer Res Ltd Proteínas de ligação específica e suas utilizações
US7742064B2 (en) * 2001-10-30 2010-06-22 Semiconductor Energy Laboratory Co., Ltd Signal line driver circuit, light emitting device and driving method thereof
US20110166319A1 (en) * 2005-02-11 2011-07-07 Immunogen, Inc. Process for preparing purified drug conjugates
CA2893252C (en) 2005-08-24 2018-05-29 Immunogen, Inc. Process for preparing antibody maytansinoid conjugates
MX338185B (es) 2007-01-25 2016-04-05 Dana Farber Cancer Inst Inc Uso de anticuerpos anti-egfr en el tratamiento de enfermedad mediada por egfr mutante.
AU2008227123B2 (en) 2007-03-15 2014-03-27 Ludwig Institute For Cancer Research Ltd. Treatment method using EGFR antibodies and src inhibitors and related formulations
JP5532486B2 (ja) 2007-08-14 2014-06-25 ルードヴィッヒ インスティテュート フォー キャンサー リサーチ Ｅｇｆ受容体を標的とするモノクローナル抗体１７５ならびにその誘導体および用途
AU2010210646B2 (en) 2009-02-05 2015-10-29 Immunogen, Inc. Novel benzodiazepine derivatives
KR102444399B1 (ko) 2009-06-03 2022-09-16 이뮤노젠 아이엔씨 메이탄시노이드의 제조방법
FR2949469A1 (fr) * 2009-08-25 2011-03-04 Sanofi Aventis Derives anticancereux, leur preparation et leur application en therapeutique
CA3014767C (en) 2010-02-24 2023-08-29 Immunogen, Inc. Folate receptor 1 antibodies and immunoconjugates and uses thereof
JP5870400B2 (ja) 2010-04-15 2016-03-01 シアトル ジェネティクス，インコーポレーテッド 標的化ピロロベンゾジアゼピンコンジュゲート
NZ602933A (en) 2010-04-15 2014-09-26 Seattle Genetics Inc Pyrrolobenzodiazepines used to treat proliferative diseases
MA34277B1 (fr) 2010-04-15 2013-06-01 Spirogen Developments Sarl Pyrrolobenzodiazépines et conjugués de celles-ci
FR2963007B1 (fr) * 2010-07-26 2013-04-05 Sanofi Aventis Derives anticancereux, leur preparation et leur application therapeutique
KR101959578B1 (ko) 2010-12-09 2019-03-18 이뮤노젠 아이엔씨 하전된 가교제의 제조방법
AU2015202826B2 (en) * 2011-02-15 2017-03-30 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
MY183977A (en) * 2011-02-15 2021-03-17 Immunogen Inc Cytotoxic benzodiazepine derivatives
CN107537040A (zh) 2011-03-29 2018-01-05 伊缪诺金公司 通过一步法制备类美登素抗体缀合物
EP2524929A1 (en) * 2011-05-17 2012-11-21 Sanofi Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of CD19+ B-cell malignancies syptoms
KR102087854B1 (ko) 2011-06-10 2020-03-12 메르사나 테라퓨틱스, 인코포레이티드 단백질-중합체-약물 접합체
US8815226B2 (en) 2011-06-10 2014-08-26 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
WO2013041606A1 (en) 2011-09-20 2013-03-28 Spirogen Sàrl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
AU2012322613B2 (en) 2011-10-14 2016-04-21 Medimmune Limited Pyrrolobenzodiazepines and targeted conjugates
EP2751111B1 (en) 2011-10-14 2017-04-26 MedImmune Limited Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases
WO2013053871A1 (en) 2011-10-14 2013-04-18 Spirogen Sàrl Pyrrolobenzodiazepines
DK2750713T3 (en) 2011-10-14 2015-12-21 Medimmune Ltd PYRROLOBENZODIAZEPINS AND CONJUGATES THEREOF
JP6393617B2 (ja) 2011-10-14 2018-09-19 シアトル ジェネティクス，インコーポレーテッド ピロロベンゾジアゼピンおよび標的コンジュゲート
EA201491173A1 (ru) * 2011-12-13 2014-11-28 Иммуноджен, Инк. Применение n-гидроксисукцинимида для улучшения стабильности конъюгатов
US9504756B2 (en) 2012-05-15 2016-11-29 Seattle Genetics, Inc. Self-stabilizing linker conjugates
HK1207388A1 (en) 2012-05-15 2016-01-29 Seattle Genetics, Inc. Self-stabilizing linker conjugates
WO2013177481A1 (en) 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
HK1211208A1 (zh) 2012-08-22 2016-05-20 Immunogen, Inc. 細胞毒性苯並二氮呯衍生物
SG11201502429YA (en) 2012-10-04 2015-04-29 Immunogen Inc Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates
JP6270859B2 (ja) 2012-10-12 2018-01-31 エイディーシー・セラピューティクス・エス・アー・エール・エルＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａｒｌ ピロロベンゾジアゼピン−抗体結合体
EP2906296B1 (en) * 2012-10-12 2018-03-21 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
JP5993093B2 (ja) 2012-10-12 2016-09-14 メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ ピロロベンゾジアゼピン類およびその複合体
US10695433B2 (en) 2012-10-12 2020-06-30 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
DK2906248T3 (en) 2012-10-12 2019-03-04 Medimmune Ltd Pyrrolobenzodiazepines and their conjugates
US9931414B2 (en) 2012-10-12 2018-04-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
WO2014057114A1 (en) 2012-10-12 2014-04-17 Adc Therapeutics Sàrl Pyrrolobenzodiazepine-anti-psma antibody conjugates
EP2906249B1 (en) 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
KR101995621B1 (ko) 2012-10-12 2019-07-03 에이디씨 테라퓨틱스 에스에이 피롤로벤조디아제핀-항-cd22 항체 컨주게이트
JP6133431B2 (ja) 2012-11-24 2017-05-24 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用
AU2013366493B2 (en) 2012-12-21 2017-08-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
HK1216176A1 (zh) 2012-12-21 2016-10-21 Medlmmune Limited 用於治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物
AU2014229529B2 (en) 2013-03-13 2018-02-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
AU2014230735B2 (en) 2013-03-13 2018-03-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
EP3441072B1 (en) 2013-03-13 2020-12-30 Seagen Inc. Activated carbon filtration for purification of benzodiazepine adcs
HK1220698A1 (zh) * 2013-03-13 2017-05-12 Seattle Genetics, Inc. 环糊精和抗体药物偶联物制剂
WO2014159981A2 (en) 2013-03-13 2014-10-02 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
EP3299391B1 (en) 2013-03-14 2019-12-04 Genentech, Inc. Anti-b7-h4 antibodies and immunoconjugates
EP2976362B1 (en) 2013-03-19 2019-10-23 Beijing Shenogen Pharma Group Ltd. Antibodies and methods for treating estrogen receptor-associated diseases
US10208125B2 (en) 2013-07-15 2019-02-19 University of Pittsburgh—of the Commonwealth System of Higher Education Anti-mucin 1 binding agents and uses thereof
US10442836B2 (en) 2013-08-12 2019-10-15 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1H-benzo[E]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
US10010624B2 (en) 2013-10-11 2018-07-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
KR102087850B1 (ko) 2013-10-11 2020-03-12 메르사나 테라퓨틱스, 인코포레이티드 단백질-고분자-약물 접합체
US9956299B2 (en) 2013-10-11 2018-05-01 Medimmune Limited Pyrrolobenzodiazepine—antibody conjugates
US10316080B2 (en) 2013-10-11 2019-06-11 Asana Biosciences, Llc Protein-polymer-drug conjugates
EP3054985B1 (en) 2013-10-11 2018-12-26 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
MX2021008464A (es) 2013-10-15 2023-03-03 Seattle Genetics Inc Farmaco-enlazadores modificados con polietilenglicol para la farmacocinetica mejorada de conjugados de ligando-farmaco.
SG11201604784XA (en) 2013-12-13 2016-07-28 Genentech Inc Anti-cd33 antibodies and immunoconjugates
BR112016013258A2 (pt) * 2013-12-16 2018-01-16 Genentech Inc composto conjugado anticorpo-droga, composição farmacêutica, método para tratar câncer e kit
ES2729057T3 (es) * 2013-12-17 2019-10-30 Aimm Therapeutics Bv Medios y métodos para contrarrestar trastornos mieloproliferativos o linfoproliferativos
CN106456725B9 (zh) 2014-02-11 2022-08-09 西雅图基因公司 蛋白质的选择性还原
US10464955B2 (en) 2014-02-28 2019-11-05 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
WO2015179658A2 (en) 2014-05-22 2015-11-26 Genentech, Inc. Anti-gpc3 antibodies and immunoconjugates
WO2016008112A1 (en) 2014-07-16 2016-01-21 Medshine Discovery Inc. Linkers and application towards adc thereof
SG11201701455SA (en) * 2014-09-03 2017-03-30 Immunogen Inc Cytotoxic benzodiazepine derivatives
TW201613930A (en) 2014-09-03 2016-04-16 Immunogen Inc Cytotoxic benzodiazepine derivatives
CN106687141A (zh) 2014-09-10 2017-05-17 麦迪穆有限责任公司 吡咯并苯并二氮杂卓及其缀合物
BR112017004802A2 (pt) 2014-09-12 2017-12-12 Genentech Inc anticorpos anti-cll-1 e imunoconjugados
CN113698485A (zh) 2014-09-12 2021-11-26 基因泰克公司 抗-b7-h4抗体及免疫缀合物
GB201416112D0 (en) 2014-09-12 2014-10-29 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
MX2017003123A (es) 2014-09-12 2017-05-12 Genentech Inc Anticuerpos y conjugados modificados geneticamente con cisteina.
PE20170935A1 (es) 2014-09-12 2017-07-13 Genentech Inc Anticuerpos anti-her2 e inmunoconjugados
SG11201702079UA (en) 2014-09-17 2017-04-27 Genentech Inc Pyrrolobenzodiazepines and antibody disulfide conjugates thereof
BR112017004953A2 (pt) * 2014-09-17 2017-12-05 Genentech Inc imunoconjugado, formulação farmacêutica, método de tratamento e método de inibição da proliferação de uma célula
BR112017011111A2 (pt) 2014-11-25 2017-12-26 Adc Therapeutics Sa conjugados de pirrolobenzodiazepina-anticorpo
CN107428780B (zh) 2015-01-14 2020-09-04 百时美施贵宝公司 苯并二氮杂*二聚体、其缀合物及制备和使用方法
JP6676058B2 (ja) 2015-01-14 2020-04-08 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ヘテロアリーレン架橋したベンゾジアゼピン二量体、そのコンジュゲート、ならびに製造および使用方法
US9504694B2 (en) * 2015-03-19 2016-11-29 Cellerant Therapeutics, Inc. Isoquinolidinobenzodiazepines
GB201506411D0 (en) 2015-04-15 2015-05-27 Bergenbio As Humanized anti-axl antibodies
GB201506402D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
EA039619B1 (ru) * 2015-05-20 2022-02-17 Иммуноджен, Инк. Способ получения индолинобензодиазепиновых соединений
GB201510010D0 (en) 2015-06-09 2015-07-22 King S College London PDD and BPD compounds
CA2989269C (en) 2015-06-15 2020-09-22 Robert Yongxin Zhao Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule
CN108391434A (zh) 2015-06-23 2018-08-10 百时美施贵宝公司 大环苯并二氮杂*二聚体、其缀合物、制备和用途
CA2988806C (en) * 2015-06-29 2024-09-10 Immunogen, Inc. MODIFIED CYSTEINE ANTIBODY CONJUGATES
EP3319936B1 (en) 2015-07-12 2025-12-17 Hangzhou Dac Biotech Co., Ltd. Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
IL286788B2 (en) 2015-07-21 2024-01-01 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
US20180339985A1 (en) 2015-08-21 2018-11-29 Femtogenix Limited Pdd compounds
GB201514928D0 (en) * 2015-08-21 2015-10-07 King S College London PDD compounds
US11078286B2 (en) 2015-09-20 2021-08-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies specific for fibroblast growth factor receptor 4 (FGFR4) and methods of their use
MA43345A (fr) 2015-10-02 2018-08-08 Hoffmann La Roche Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation
MA43354A (fr) 2015-10-16 2018-08-22 Genentech Inc Conjugués médicamenteux à pont disulfure encombré
ES2970186T3 (es) 2015-11-25 2024-05-27 Immunogen Inc Formulaciones farmacéuticas y métodos de uso de las mismas
ES2919323T3 (es) 2015-12-04 2022-07-26 Seagen Inc Conjugados de compuestos de tubulisina cuaternizados
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
GB201601431D0 (en) 2016-01-26 2016-03-09 Medimmune Ltd Pyrrolobenzodiazepines
GB201602359D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
GB201602356D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
CN109843919A (zh) 2016-03-25 2019-06-04 西雅图基因公司 用于制备聚乙二醇化的药物-接头及其中间体的方法
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
FR3049605B1 (fr) * 2016-04-05 2018-03-23 Arkema France Procede d'obtention de films fins et articles filmogenes
CA3021098A1 (en) 2016-04-21 2017-10-26 Abbvie Stemcentrx Llc Novel anti-bmpr1b antibodies and methods of use
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
WO2017196847A1 (en) 2016-05-10 2017-11-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Variable new antigen receptor (vnar) antibodies and antibody conjugates targeting tumor and viral antigens
WO2017201132A2 (en) 2016-05-18 2017-11-23 Mersana Therapeutics, Inc. Pyrrolobenzodiazepines and conjugates thereof
JP7022080B2 (ja) 2016-05-27 2022-02-17 ジェネンテック， インコーポレイテッド 部位特異的抗体－薬物複合体の特徴付けのための生化学分析的方法
WO2017214182A1 (en) 2016-06-07 2017-12-14 The United States Of America. As Represented By The Secretary, Department Of Health & Human Services Fully human antibody targeting pdi for cancer immunotherapy
WO2017223275A1 (en) 2016-06-24 2017-12-28 Mersana Therapeutics, Inc. Pyrrolobenzodiazepines and conjugates thereof
EP3494135A1 (en) 2016-08-02 2019-06-12 The United States of America, as represented by The Secretary, Department of Health and Human Services Monoclonal antibodies targeting glypican-2 (gpc2) and use thereof
TWI851531B (zh) 2016-08-09 2024-08-11 美商思進公司 具有改善之生理化學性質之具自我穩定連接子之藥物結合物
JP7093767B2 (ja) 2016-08-11 2022-06-30 ジェネンテック， インコーポレイテッド ピロロベンゾジアゼピンプロドラッグ及びその抗体コンジュゲート
EP3522932A4 (en) 2016-10-10 2020-06-24 Cellerant Therapeutics, Inc. ISOCHINOLIDINOBENZODIAZEPINE (IQB) -1 (CHLORMETHYL) -2,3-DIHYDRO-1-H-BENZO [E] INDOL (CBI) DIMERS
GB201617466D0 (en) 2016-10-14 2016-11-30 Medimmune Ltd Pyrrolobenzodiazepine conjugates
JP2020500214A (ja) * 2016-11-02 2020-01-09 イミュノジェン・インコーポレーテッド 抗体薬物複合体とｐａｒｐ阻害剤との併用治療
KR20220147721A (ko) 2016-11-14 2022-11-03 항저우 디에이씨 바이오테크 씨오, 엘티디 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용
JP7313684B2 (ja) 2016-11-21 2023-07-25 キュレアブ ゲーエムベーハー 抗ｇｐ７３抗体及びイムノコンジュゲート
US10287256B2 (en) 2016-11-23 2019-05-14 Immunogen, Inc. Selective sulfonation of benzodiazepine derivatives
JP7244987B2 (ja) 2016-12-14 2023-03-23 シージェン インコーポレイテッド 多剤抗体薬物コンジュゲート
MA50134A (fr) 2016-12-16 2020-07-29 Bluefin Biomedicine Inc Anticorps anti-protéine 1 contenant un domaine anti-cub (cdcp1), conjugués anticorps-médicament et leurs méthodes d'utilisation
AU2017382883B2 (en) 2016-12-21 2024-07-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibodies specific for FLT3 and uses thereof
HRP20220550T1 (hr) 2016-12-23 2022-06-10 Immunogen, Inc. Imunokonjugati koji ciljaju adam9 i postupci njihove uporabe
TW201825515A (zh) 2017-01-04 2018-07-16 美商伊繆諾金公司 Ｍｅｔ抗體以及其免疫結合物及用途
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
HUE054689T2 (hu) 2017-02-08 2021-09-28 Adc Therapeutics Sa Pirrolobenzodiazepin-antitest konjugátumok
CN110430901B (zh) 2017-03-24 2024-08-16 西雅图基因公司 制备葡糖苷酸药物-接头及其中间体的方法
SI3612537T1 (sl) 2017-04-18 2022-10-28 Medimmune Limited Konjugati pirolobenzodiazepina
EP3612234B1 (en) 2017-04-20 2024-03-13 ADC Therapeutics SA Combination therapy with an anti-axl antibody-drug conjugate
CN110573510B (zh) 2017-04-20 2022-10-11 伊缪诺金公司 制备吲哚啉并苯并二氮杂䓬衍生物的方法
US11026947B2 (en) 2017-04-27 2021-06-08 The Brigham And Women's Hospital, Inc. ALK2 inhibitors and methods for inhibiting BMP signaling
EP3625256A1 (en) 2017-05-19 2020-03-25 The U.S.A. as represented by the Secretary, Department of Health and Human Services Human monoclonal antibody targeting tnfr2 for cancer immunotherapy
CA3064804A1 (en) 2017-06-14 2018-12-20 Adc Therapeutics Sa Dosage regimes for the administration of an anti-cd19 adc
CA3066953A1 (en) 2017-06-30 2019-01-03 Lentigen Technology, Inc. Human monoclonal antibodies specific for cd33 and methods of their use
WO2019005208A1 (en) 2017-06-30 2019-01-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services ANTIBODIES TO HUMAN MESOTHELIN AND USES IN ANTICANCER THERAPY
EP3658172A4 (en) 2017-07-25 2021-05-05 TrueBinding, Inc. TREATING CANCER BY BLOCKING THE INTERACTION OF TIM-3 AND HIS LIGAND
SG11202000358YA (en) 2017-08-18 2020-02-27 Medimmune Ltd Pyrrolobenzodiazepine conjugates
TWI885539B (zh) 2017-09-29 2025-06-01 日商第一三共股份有限公司 抗體－吡咯并苯二氮呯衍生物複合體
EP3717021A1 (en) 2017-11-27 2020-10-07 Mersana Therapeutics, Inc. Pyrrolobenzodiazepine antibody conjugates
TWI827575B (zh) * 2017-12-28 2024-01-01 美商伊繆諾金公司 苯二氮平衍生物
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
MX2020012718A (es) 2018-05-29 2021-02-16 Intocell Inc Derivados de benzodiazepinas novedosos y usos de los mismos.
WO2020014482A1 (en) 2018-07-12 2020-01-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Affinity matured cd22-specific monoclonal antibody and uses thereof
CA3106544A1 (en) 2018-08-08 2020-02-13 Mitchell Ho High affinity monoclonal antibodies targeting glypican-2 and uses thereof
TWI897855B (zh) 2018-10-26 2025-09-21 美商免疫遺傳股份有限公司 Ｅ ｐ Ｃ Ａ Ｍ 抗體、可活化抗體及免疫偶聯物以及其用途
US12274898B2 (en) 2018-10-31 2025-04-15 Intocell, Inc. Substituted benzodiazepines as antibody-drug conjugates
IL319265A (en) 2018-12-21 2025-04-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and their uses
CA3125484A1 (en) 2019-01-08 2020-07-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Cross-species single domain antibodies targeting mesothelin for treating solid tumors
EP3883971A1 (en) 2019-01-22 2021-09-29 The United States of America, as represented by the Secretary, Department of Health and Human Services High affinity monoclonal antibodies targeting glypican-1 and methods of use
CN120058944A (zh) 2019-01-30 2025-05-30 真和制药有限公司 抗gal3抗体及其用途
MX2021010477A (es) 2019-03-15 2021-10-01 Medimmune Ltd Dimeros de azetidobenzodiazepina y conjugados que los comprenden para uso en el tratamiento de cancer.
TW202102506A (zh) * 2019-03-29 2021-01-16 美商伊繆諾金公司 苯二氮平衍生物
SG11202113331QA (en) * 2019-06-04 2021-12-30 Magenta Therapeutics Inc Methods and compositions for treating autoimmune diseases
CN119899265A (zh) 2019-10-22 2025-04-29 美国政府(由卫生和人类服务部的部长所代表) 用于治疗多种实体瘤的靶向b7h3（cd276）的高亲和力纳米抗体
US20230094463A1 (en) 2019-12-06 2023-03-30 Truebinding, Inc. Antibodies that disrupt the interaction of gal3 and insulin receptor or integrins and methods of use thereof
AU2020402752A1 (en) 2019-12-12 2022-06-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Antibody-drug conjugates specific for CD276 and uses thereof
TW202144572A (zh) 2020-03-19 2021-12-01 美商亞維代堤生物科學公司 治療臉肩胛肱骨肌肉失養症之組合物及方法
BR112022019137A2 (pt) 2020-03-27 2023-01-31 Avidity Biosciences Inc Composições e métodos de tratamento de distrofia muscular
BR112022020332A2 (pt) 2020-04-10 2022-12-13 Seagen Inc Composto conjugado anticorpo-droga, composição, método de tratamento de câncer e de um distúrbio autoimune
WO2021222875A1 (en) 2020-04-30 2021-11-04 Keros Therapeutics, Inc. Methods of using alk2 inhibitors
MX2022014786A (es) 2020-05-26 2023-01-16 Truebinding Inc Metodos para tratar enfermedades inflamatorias mediante el bloqueo de galectina-3.
CN111646999A (zh) * 2020-07-30 2020-09-11 内江师范学院 一种吲哚啉羧酸类化合物及其制备方法
WO2022082058A1 (en) * 2020-10-16 2022-04-21 Eleusis Therapeutics Us, Inc. Method of treatment by tryptamine alkaloids
WO2022093745A1 (en) 2020-10-26 2022-05-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Single domain antibodies targeting sars coronavirus spike protein and uses thereof
WO2022098812A1 (en) 2020-11-04 2022-05-12 Keros Therapeutics, Inc. Methods of treating iron overload
JP2024511360A (ja) 2021-03-18 2024-03-13 シージェン インコーポレイテッド 生体活性化合物の内部移行複合体からの選択的薬物放出
AU2022238571A1 (en) 2021-03-18 2023-09-14 Seagen Inc. Selective drug release from internalized conjugates of biologically active compounds
WO2022232612A1 (en) 2021-04-29 2022-11-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lassa virus-specific nanobodies and methods of their use
US20240270851A1 (en) 2021-06-09 2024-08-15 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Cross species single domain antibodies targeting pd-l1 for treating solid tumors
WO2023288252A1 (en) 2021-07-13 2023-01-19 Truebinding, Inc. Methods of preventing protein aggregation
WO2023018960A1 (en) 2021-08-13 2023-02-16 Immunogen, Inc. Improved methods for preparing cytotoxic benzodiazepine derivatives
CA3231330A1 (en) 2021-09-16 2023-03-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
AU2021362997A1 (en) 2021-11-03 2024-05-16 Hangzhou Dac Biotech Co., Ltd. Specific conjugation of an antibody
AU2022388722A1 (en) 2021-11-09 2024-05-23 Truebinding, Inc. Methods of treating or inhibiting cardiovascular diseases
CN119137157A (zh) 2022-05-03 2024-12-13 基因泰克公司 抗Ly6E抗体、免疫缀合物及其用途
US20250367307A1 (en) 2022-06-30 2025-12-04 Toray Industries, Inc. Pharmaceutical composition for cancer treatment and/or prevention
WO2024129756A1 (en) 2022-12-13 2024-06-20 Seagen Inc. Site-specific engineered cysteine antibody drug conjugates
WO2024258995A2 (en) * 2023-06-13 2024-12-19 Delix Therapeutics, Inc. Fused tetrahydroazepine psychoplastogens and uses thereof
WO2025019228A1 (en) 2023-07-20 2025-01-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Fully human monoclonal antibodies and chimeric antigen receptors against cd276 for the treatment of solid tumors
EP4509142A1 (en) 2023-08-16 2025-02-19 Ona Therapeutics S.L. Fgfr4 as target in cancer treatment
WO2025149947A1 (en) 2024-01-12 2025-07-17 Seagen Inc. Antibody-drug conjugates
WO2025171238A1 (en) 2024-02-07 2025-08-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies that bind the juxta-membrane region of mesothelin and uses thereof

Family Cites Families (108)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US860600A (en) * 1900-05-07 1907-07-16 U S Standard Voting Machine Company Interlocking mechanism.
SU11248A1 (ru) 1927-03-29 1929-09-30 В.С. Григорьев Способ очистки антрацена
US3453266A (en) 1966-03-14 1969-07-01 American Home Prod 1,2,5-benzothiadiazepine 1,1-dioxides
US3506646A (en) 1966-06-27 1970-04-14 American Home Prod Process for the preparation of 7h-pyrido (1,2-b)(1,2,5)benzothiadiazepine 5,5 - dioxides and pyrrolo(1,2-b)(1,2,5)benzothiadiazepine 5,5-dioxides
US3763183A (en) * 1972-07-10 1973-10-02 Sterling Drug Inc 1,2,3,10,11,11a-hexahydro-5h-pyrrolo (2,1-c)(1,4)benzodiazepines
US3860600A (en) * 1972-07-10 1975-01-14 Sterling Drug Inc Octahydropyrrido{8 2,1-c{9 {8 1,4{9 benzodiazepines
US3875162A (en) 1973-07-26 1975-04-01 Squibb & Sons Inc Certain 6H-pyrimido{8 1,2-c{9 {8 1,3,5{9 benzothiadiaza compounds
US4003905A (en) 1974-12-11 1977-01-18 E. R. Squibb & Sons, Inc. Diels-alder adducts of benzdiazepines
JPS57131791A (en) * 1980-12-31 1982-08-14 Fujisawa Pharmaceut Co Ltd Benzodiazepine derivative and its preparation
US4444688A (en) 1981-05-11 1984-04-24 Ciba-Geigy Corporation Imidazobenzothiadiazepines
US4678784A (en) * 1984-04-11 1987-07-07 Mcneilab, Inc. Method for the treatment of LHRH diseases and conditions
US4928908A (en) 1987-06-12 1990-05-29 Reiko Co., Ltd. Balloon made of metal vapor deposited film
FR2633167B1 (fr) 1988-06-27 1990-09-21 Oreal Ensemble applicateur d'un produit en poudre ou pateux notamment d'un produit cosmetique
JP2920385B2 (ja) 1988-08-18 1999-07-19 武田薬品工業株式会社 １，２，５‐ベンゾチアジアゼピン誘導体，その製造法および用途
GB8827305D0 (en) 1988-11-23 1988-12-29 British Bio Technology Compounds
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
DE69233782D1 (de) 1991-12-02 2010-05-20 Medical Res Council Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken
ATE398176T1 (de) * 1991-12-06 2008-07-15 Max Planck Gesellschaft Phosphorylierungsepitope aus dem tau-protein zur diagnose und behandlung der alzheimer-krankheit
GB9205051D0 (en) * 1992-03-09 1992-04-22 Cancer Res Campaign Tech Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them
ES2149768T3 (es) 1992-03-25 2000-11-16 Immunogen Inc Conjugados de agentes enlazantes de celulas derivados de cc-1065.
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5455258A (en) 1993-01-06 1995-10-03 Ciba-Geigy Corporation Arylsulfonamido-substituted hydroxamic acids
JPH08176070A (ja) 1994-12-19 1996-07-09 Mitsubishi Chem Corp ジデプシド誘導体及びｐｉ３キナーゼ阻害剤
JPH08175990A (ja) 1994-12-19 1996-07-09 Mitsubishi Chem Corp Ｐｉ３キナーゼ阻害剤とその製造法
US5863949A (en) 1995-03-08 1999-01-26 Pfizer Inc Arylsulfonylamino hydroxamic acid derivatives
US5861510A (en) 1995-04-20 1999-01-19 Pfizer Inc Arylsulfonyl hydroxamic acid derivatives as MMP and TNF inhibitors
GB9521987D0 (en) 1995-10-26 1996-01-03 Ludwig Inst Cancer Res Phosphoinositide 3-kinase modulators
GB9624482D0 (en) 1995-12-18 1997-01-15 Zeneca Phaema S A Chemical compounds
DE69624081T2 (de) 1995-12-20 2003-06-12 Agouron Pharmaceuticals, Inc. Matrix-metalloprotease Inhibitoren
AU719434B2 (en) 1996-02-13 2000-05-11 Astrazeneca Ab Quinazoline derivatives as VEGF inhibitors
ES2169355T3 (es) 1996-03-05 2002-07-01 Astrazeneca Ab Derivados de 4-anilinoquinazolina.
EP0818442A3 (en) 1996-07-12 1998-12-30 Pfizer Inc. Cyclic sulphone derivatives as inhibitors of metalloproteinases and of the production of tumour necrosis factor
EA199900036A1 (ru) 1996-07-18 1999-06-24 Пфайзер Инк Ингибиторы металлопротеаз матрикса на основе фосфинатов, фармацевтическая композиция, способ лечения
PL331895A1 (en) 1996-08-23 1999-08-16 Pfizer Arylosulphonylamino derivatives of hydroxamic acid
GB9718972D0 (en) 1996-09-25 1997-11-12 Zeneca Ltd Chemical compounds
DK0950059T3 (da) 1997-01-06 2004-11-01 Pfizer Cycliske sulfonderivater
ATE248812T1 (de) 1997-02-03 2003-09-15 Pfizer Prod Inc Arylsulfonylhydroxamsäurederivate
JP2000507975A (ja) 1997-02-07 2000-06-27 ファイザー・インク Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用
PL334997A1 (en) 1997-02-11 2000-03-27 Pfizer Derivatives or arylosulphonyl-hydroxamic acid
DK0961780T3 (da) 1997-02-12 2007-08-27 Electrophoretics Ltd Proteinmarkörer for lungecancer og anvendelse deraf
JP2002501721A (ja) 1997-08-01 2002-01-22 モルフォシス・アクチェンゲゼルシャフト 多量体（ポリ）ペプチドコンプレックスのメンバーをコードする核酸配列を同定するための新規方法およびファージ
BR9811868A (pt) 1997-08-08 2000-08-15 Pfizer Prod Inc Derivados de ácido ariloxiarilsulfonilamino hidroxâmico
GB9725782D0 (en) 1997-12-05 1998-02-04 Pfizer Ltd Therapeutic agents
GB9801690D0 (en) 1998-01-27 1998-03-25 Pfizer Ltd Therapeutic agents
JP4462654B2 (ja) 1998-03-26 2010-05-12 ソニー株式会社 映像素材選択装置及び映像素材選択方法
PA8469401A1 (es) 1998-04-10 2000-05-24 Pfizer Prod Inc Derivados biciclicos del acido hidroxamico
PA8469501A1 (es) 1998-04-10 2000-09-29 Pfizer Prod Inc Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico
US6156746A (en) 1998-08-25 2000-12-05 Bristol-Myers Squibb Company 1,2,5-benzothiadiazepine-1,1-dioxides with n-2 imidazolylalkyl substituents
DE69907977T2 (de) * 1998-08-27 2004-07-22 Spirogen Ltd., Ryde Pyrrolobenzodiazepine
GB9818731D0 (en) * 1998-08-27 1998-10-21 Univ Portsmouth Compounds
ES2213985T3 (es) 1998-11-05 2004-09-01 Pfizer Products Inc. Derivados de hidroxiamida de acido 5-oxo-pirrolidin-2-carboxilico.
MXPA01008182A (es) 1999-02-10 2003-08-20 Astrazeneca Ab Derivados de quinazolina como inhibidores de angiotensina.
EP1676845B1 (en) 1999-11-05 2008-06-11 AstraZeneca AB New quinazoline derivatives
HK1049997B (en) 1999-11-24 2007-02-23 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use
PT1255752E (pt) 2000-02-15 2007-10-17 Pharmacia & Upjohn Co Llc Inibidores de proteína quinases: 2-indolinonas substituídas com pirrolo
JP2001247477A (ja) 2000-03-03 2001-09-11 Teikoku Hormone Mfg Co Ltd 抗腫瘍剤
US6403588B1 (en) 2000-04-27 2002-06-11 Yamanouchi Pharmaceutical Co., Ltd. Imidazopyridine derivatives
US6608053B2 (en) 2000-04-27 2003-08-19 Yamanouchi Pharmaceutical Co., Ltd. Fused heteroaryl derivatives
JP2003534384A (ja) 2000-05-26 2003-11-18 オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド 神経保護性ペプチド
JP4458746B2 (ja) 2001-01-16 2010-04-28 グラクソ グループ リミテッド 癌の治療方法
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
EP1417976A4 (en) 2001-07-26 2004-09-15 Santen Pharmaceutical Co Ltd AGENT FOR TREATING GLAUKOM WITH A COMPOUND WITH PI3-KINASE INHIBITING EFFECT
US6703414B2 (en) 2001-09-14 2004-03-09 Arizona Board Of Regents On Behalf Of The University Of Arizona Device and method for treating restenosis
US6894055B2 (en) 2001-10-24 2005-05-17 Iconix Pharmaceuticals Inc. Thieno-2′,3′ -5,6pyrimido[3,4-A]-1,2,4-triazole derivatives as modulators of phoshoinositide 3-kinase
WO2003035618A2 (en) 2001-10-24 2003-05-01 Iconix Pharmaceuticals, Inc. Modulators of phosphoinositide 3-kinase
BR0213734A (pt) 2001-10-30 2004-10-19 Pharmacia Corp Derivados de carboxamida heteroaromático para o tratamento de inflamação
US6716821B2 (en) 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
GB0209467D0 (en) 2002-04-25 2002-06-05 Astrazeneca Ab Chemical compounds
US20050276812A1 (en) 2004-06-01 2005-12-15 Genentech, Inc. Antibody-drug conjugates and methods
US7538195B2 (en) 2002-06-14 2009-05-26 Immunogen Inc. Anti-IGF-I receptor antibody
CA2493843C (en) 2002-07-10 2012-04-17 Applied Research Systems Ars Holding N.V. Azolidinone-vinyl fused-benzene derivatives
CA2489779A1 (en) 2002-07-10 2004-01-22 Applied Research Systems Ars Holding N.V. Use of compounds for increasing spermatozoa motility
US20040092561A1 (en) 2002-11-07 2004-05-13 Thomas Ruckle Azolidinone-vinyl fused -benzene derivatives
BR0313197A (pt) 2002-08-02 2005-08-09 Immunogen Inc Agentes citotóxicos contendo potentes taxanos e seu uso terapêutico
ATE499116T1 (de) 2002-08-16 2011-03-15 Immunogen Inc Vernetzer mit hoher reaktivität und löslichkeit und ihre verwendung bei der herstellung von konjugaten für die gezielte abgabe von kleinmolekularen arzneimitteln
WO2004017950A2 (en) 2002-08-22 2004-03-04 Piramed Limited Phosphadidylinositol 3,5-biphosphate inhibitors as anti-viral agents
FR2850654A1 (fr) 2003-02-03 2004-08-06 Servier Lab Nouveaux derives d'azepines tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
DE60326060D1 (de) * 2003-03-31 2009-03-19 Council Scient Ind Res Nichtvernetzende pyrroloä2,1-cüä1,4übenzodiazepine als potentielle antitumor-agentien und ihre herstellung
RU2338747C2 (ru) * 2003-03-31 2008-11-20 Каунсил Оф Сайентифик Энд Индастриал Рисерч ДИМЕРЫ ПИРРОЛО [2, 1-c][1, 4] БЕНЗОДИАЗЕПИНА В КАЧЕСТВЕ ПРОТИВООПУХОЛЕВЫХ СРЕДСТВ И СПОСОБ ИХ ПОЛУЧЕНИЯ
EP1608663B1 (en) 2003-03-31 2008-11-05 Council of Scientific and Industrial Research Pyrrolo (2,1-c)(1,4) benzodiazepines dimers as antitumour agents and process thereof
RU2314309C2 (ru) * 2003-03-31 2008-01-10 Каунсил Оф Сайентифик Энд Индастриал Рисерч Пирроло [2.1-c][1.4] бензодиазепины, способ их получения и фармацевтическая композиция на их основе
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
ATE516288T1 (de) * 2003-10-22 2011-07-15 Us Gov Health & Human Serv Pyrrolobenzodiazepinderivate, zusammensetzungen, die diese enthalten, und damit in zusammenhang stehende verfahren
GB0404578D0 (en) * 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
US7528126B2 (en) 2004-03-09 2009-05-05 Spirogen Limited Pyrrolobenzodiazepines
GB0410725D0 (en) * 2004-05-13 2004-06-16 Spirogen Ltd Pyrrolobenzodiazepine therapeutic agents
GB0423653D0 (en) 2004-10-25 2004-11-24 Piramed Ltd Pharmaceutical compounds
AU2005316844A1 (en) 2004-11-29 2006-06-22 Seattle Genetics, Inc. Engineered antibodies and immunoconjugates
ITRM20050416A1 (it) 2005-08-03 2007-02-04 Uni Degli Studi Di Roma Tor Vergata Derivati delle benzodiazepine e loro usi in campo medico.
WO2007039752A1 (en) * 2005-10-05 2007-04-12 Spirogen Limited Alkyl 4- [4- (5-oxo-2, 3, 5, 11a-tetrahyd0-5h-pyrr0l0 [2, 1-c] [1, 4] benzodiazepine-8-yloxy) -butyrylamino]-1h-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease
GB0520657D0 (en) 2005-10-11 2005-11-16 Ludwig Inst Cancer Res Pharmaceutical compounds
EP1813614B1 (en) 2006-01-25 2011-10-05 Sanofi Cytotoxic agents comprising new tomaymycin derivatives
DE112007000079B4 (de) * 2006-02-13 2015-08-13 Council Of Scientific & Industrial Research Neuartige Bis-Pyrrolo[2,1-c][1,4]benzodiazepin-anthrachinon Konjugate und ein Verfahren zu deren Herstellung
EP1864682A1 (en) 2006-06-09 2007-12-12 Sanofi-Aventis Leptomycin derivatives
PT2019104E (pt) 2007-07-19 2013-12-03 Sanofi Sa Agentes citotóxicos compreendendo novos derivados de tomaimicina e sua utilização terapêutica
WO2009016647A1 (en) 2007-08-01 2009-02-05 Council Of Scientific & Industrial Research Pyrrolo [2,1-c][1, 4] benzodiazepine-glycoside prodrugs useful as a selective anti tumor agent
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
AU2010210646B2 (en) 2009-02-05 2015-10-29 Immunogen, Inc. Novel benzodiazepine derivatives
EP2486023A4 (en) 2009-10-06 2014-05-07 Immunogen Inc EFFICIENT CONJUGATES AND HYDROPHILIC BINDER
CA3014767C (en) 2010-02-24 2023-08-29 Immunogen, Inc. Folate receptor 1 antibodies and immunoconjugates and uses thereof
JP5870400B2 (ja) 2010-04-15 2016-03-01 シアトル ジェネティクス，インコーポレーテッド 標的化ピロロベンゾジアゼピンコンジュゲート
NZ602933A (en) 2010-04-15 2014-09-26 Seattle Genetics Inc Pyrrolobenzodiazepines used to treat proliferative diseases
MA34277B1 (fr) 2010-04-15 2013-06-01 Spirogen Developments Sarl Pyrrolobenzodiazépines et conjugués de celles-ci
MY183977A (en) 2011-02-15 2021-03-17 Immunogen Inc Cytotoxic benzodiazepine derivatives
HK1211208A1 (zh) 2012-08-22 2016-05-20 Immunogen, Inc. 細胞毒性苯並二氮呯衍生物

Also Published As

Publication number Publication date
SG173152A1 (en) 2011-08-29
KR20110120308A (ko) 2011-11-03
EP3360879A1 (en) 2018-08-15
CA2750519A1 (en) 2010-08-12
BRPI1008749A2 (pt) 2015-08-25
US20180355055A1 (en) 2018-12-13
IL241632B (en) 2020-07-30
ZA201105352B (en) 2014-09-25
JP6581630B2 (ja) 2019-09-25
US20210238301A1 (en) 2021-08-05
ES2604668T3 (es) 2017-03-08
EP3100745A1 (en) 2016-12-07
JP2015187144A (ja) 2015-10-29
IL295601B2 (en) 2024-11-01
AU2010210646A1 (en) 2011-08-11
KR102021728B1 (ko) 2019-09-16
RU2545080C2 (ru) 2015-03-27
RU2015103852A3 (pt) 2018-09-24
CN102365021B (zh) 2015-07-15
US20160222013A1 (en) 2016-08-04
EP2393362B1 (en) 2016-08-24
US20130302357A1 (en) 2013-11-14
US20190276552A1 (en) 2019-09-12
US8802667B2 (en) 2014-08-12
JP5977522B2 (ja) 2016-08-24
RU2011136686A (ru) 2013-03-20
US8426402B2 (en) 2013-04-23
US11505617B2 (en) 2022-11-22
KR20190060009A (ko) 2019-05-31
NZ594177A (en) 2014-02-28
CN105175434A (zh) 2015-12-23
IL241634B (en) 2020-03-31
NZ620649A (en) 2015-09-25
KR101835033B1 (ko) 2018-03-08
IL295601A (en) 2022-10-01
WO2010091150A1 (en) 2010-08-12
EP2393362A1 (en) 2011-12-14
US8809320B2 (en) 2014-08-19
RU2015103852A (ru) 2015-11-10
US10208127B2 (en) 2019-02-19
US20170183419A1 (en) 2017-06-29
IL241634A0 (en) 2015-11-30
JP2015017095A (ja) 2015-01-29
US20180079823A1 (en) 2018-03-22
EP2393362A4 (en) 2013-07-24
KR20180027613A (ko) 2018-03-14
IL271761B (en) 2022-09-01
US9265841B2 (en) 2016-02-23
EP3100745B1 (en) 2018-04-18
CN105198908A (zh) 2015-12-30
AU2010210646B2 (en) 2015-10-29
US20100203007A1 (en) 2010-08-12
MX368362B (es) 2019-09-30
BRPI1008749B1 (pt) 2020-12-22
IL241633A0 (en) 2015-11-30
IL214475A (en) 2015-10-29
CN108727407A (zh) 2018-11-02
JP6204294B2 (ja) 2017-09-27
CN102365021A (zh) 2012-02-29
MX2011008328A (es) 2011-11-04
RU2019108153A (ru) 2020-09-22
US10947315B2 (en) 2021-03-16
US20150030616A1 (en) 2015-01-29
IL241632A0 (en) 2015-11-30
CA2750519C (en) 2018-09-25
IL295601B1 (en) 2024-07-01
IL214475A0 (en) 2011-09-27
US20130266596A1 (en) 2013-10-10
SG2014009138A (en) 2014-03-28
CN105198908B (zh) 2019-12-24
CA3014224A1 (en) 2010-08-12
US9550787B2 (en) 2017-01-24
CA3014224C (en) 2022-05-24
SG10201706294VA (en) 2017-09-28
KR101984053B1 (ko) 2019-05-30
RU2683325C2 (ru) 2019-03-28
JP2012516896A (ja) 2012-07-26
IL271761A (en) 2020-02-27
CN108727407B (zh) 2022-01-28
JP2018021056A (ja) 2018-02-08

Similar Documents

Publication Publication Date Title
BRPI1008749B8 (pt) compostos derivados de benzodiazepina, seus conjugados, composição farmacêutica, seu uso e seus processos de preparação
CO6612267A2 (es) Nuevos derivados de 1,1 dióxido- 5 fenil- 2,3,4-5tetrahidro- 1,4-benzotiazepina y composiciones farmaceúticas que los comprenden
IL205490A (en) 8-phenylamino-imidazo [1, a5] pyridines and pharmaceuticals containing them to inhibit abnormal cell growth
EA201491394A1 (ru) Макроциклические производные для лечения пролиферативных заболеваний
BR112014015720A8 (pt) derivados de tieno[3,2-d]pirimidina que têm atividade inibidora de proteinas quinases
CR10287A (es) Derivados de octahidro -pirrolo [3,4-b]pirrol
Jang et al. TM‐25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co‐activator TAZ
NZ609448A (en) Tricyclic pi3k inhibitor compounds and methods of use
ECSP11011185A (es) Compuestos orgánicos
BRPI0913580B8 (pt) compostos de pirrolopiridinas como inibidores de quinase e composição farmacêutica compreendendo os referidos compostos
WO2010003022A8 (en) Isoindolone derivatives as mek kinase inhibitors and methods of use
GEAP202215630A (en) 2,3-dihydro-1h-pyrrolo[3,4-c]pyridin-1-one derivatives as hpk1 inhibitors for the treatment of cancer
NZ631187A (en) Tricyclic quinoline and quinoxaline derivatives
EA201490859A1 (ru) Алкилированные соединения пиперазина в качестве ингибиторов тирозинкиназы брутона
BRPI0709680B8 (pt) derivados de pirrol, tiofeno e furano substituídos por piridil e piridimil como inibidores de quinase
EP2558092A1 (en) Combination comprising a cyclin dependent kinase 4 or cyclin dependent kinase (cdk4/6) inhibitor and an mtor inhibitor for treating cancer
BR112013024122A2 (pt) compostos de benzoxazepina seletivos para p110 delta pi3k e métodos de uso
NO20084928L (no) Farmasoytiske sammensetninger
BRPI0517461A (pt) compostos farmacêuticos
BR112013018515A2 (pt) derivados de pirrol tricíclico, processo para preparação e seu uso como inibidores da quinase
CU20140023A7 (es) DERIVADOS DE N-(3-(1,2,4-OXADIAZOL-3/5-IL)FENIL)IMIDAZO[1,2-a]PIRIDIN-3-CARBOXAMIDA COMO INHIBIDORES DE LA QUINASA c-Kit
NO20084927L (no) Fosfoinositid-3-kinaseinhibitorforbindelser og farmasoytiske sammensetninger inneholdende dem
MX2012000166A (es) Compuestos de quinazolina que contienen fosforo y metodos de uso de los mismos.
BR112015029972A2 (pt) composto, composição farmacêutica, processo para a preparação de uma composição farmacêutica, método para o tratamento de uma doença, conjunto e utilização de um composto
BR112015002493A8 (pt) composto, composição farmacêutica, processo para a preparação de uma composição farmacêutica, kit e uso de um composto”

Legal Events

Date Code Title Description
B07D Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]
B06F Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]
B07E Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]
B06U Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]
B06A Patent application procedure suspended [chapter 6.1 patent gazette]
B09A Decision: intention to grant [chapter 9.1 patent gazette]
B16A Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]

Free format text: PRAZO DE VALIDADE: 10 (DEZ) ANOS CONTADOS A PARTIR DE 22/12/2020, OBSERVADAS AS CONDICOES LEGAIS.

B16C Correction of notification of the grant [chapter 16.3 patent gazette]

Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 04/02/2010 OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF

B21F Lapse acc. art. 78, item iv - on non-payment of the annual fees in time

Free format text: REFERENTE A 16A ANUIDADE.