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PE20171184A1 - Dimeros de benzodiazepina, conjugados de estos, y sus metodos de preparacion y uso - Google Patents

Dimeros de benzodiazepina, conjugados de estos, y sus metodos de preparacion y uso

Info

Publication number
PE20171184A1
PE20171184A1 PE2017001216A PE2017001216A PE20171184A1 PE 20171184 A1 PE20171184 A1 PE 20171184A1 PE 2017001216 A PE2017001216 A PE 2017001216A PE 2017001216 A PE2017001216 A PE 2017001216A PE 20171184 A1 PE20171184 A1 PE 20171184A1
Authority
PE
Peru
Prior art keywords
conjugates
preparation
methods
independently
dimer
Prior art date
Application number
PE2017001216A
Other languages
English (en)
Inventor
Yong Zhang
Ivar M Mcdonald
Naidu S Chowdari
Tram N Huynh
Robert M Borzilleri
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of PE20171184A1 publication Critical patent/PE20171184A1/es

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    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/6843—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 material from animals or humans
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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

Abstract

Se refiere a un dimero de benzodiazepina de formula (I), en donde R1 es de formula (Ia) o (Ib); cada G y G´ son C o N, siempre que no mas de dos G o dos G´ sean N; R2 es H o C1-C5-alquilo; R3 y R4 son, independientemente, H, F, Cl, entre otros; cada linea doble en un sistema de anillos de diazepina representa un enlace simple o doble; R5 es H si la linea doble al N al cual esta unido, es un enlace simple y esta ausente si la linea doble es un enlace doble; R6 es H, OH, entre otros; R7, R8, R9 y R10 es, independientemente, H, C1-C5 alquilo, C?C(CH2)15X2, entre otros; o si un R7, R8, R9 y R10 esta unido a G o G´ que es N, estara ausente; cada Y es, independientemente, CH2, C=O o CHR12. Tambien se refiere a un conjugado que contiene el citado dimero con un anticuerpo y a una formulacion farmaceutica que lo comprende. Dicho dimero es util como agente antineoplasico, especialmente como un conjugado anticuerpo-farmaco (ADC)
PE2017001216A 2015-01-14 2016-01-13 Dimeros de benzodiazepina, conjugados de estos, y sus metodos de preparacion y uso PE20171184A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562103157P 2015-01-14 2015-01-14
US201562215928P 2015-09-09 2015-09-09

Publications (1)

Publication Number Publication Date
PE20171184A1 true PE20171184A1 (es) 2017-08-22

Family

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PE2017001216A PE20171184A1 (es) 2015-01-14 2016-01-13 Dimeros de benzodiazepina, conjugados de estos, y sus metodos de preparacion y uso

Country Status (19)

Country Link
US (4) US9527871B2 (es)
EP (1) EP3245213B1 (es)
JP (1) JP6498773B2 (es)
KR (1) KR20170102980A (es)
CN (1) CN107428780B (es)
AU (1) AU2016206798A1 (es)
BR (1) BR112017014599A2 (es)
CA (1) CA2973354A1 (es)
CL (1) CL2017001824A1 (es)
CO (1) CO2017008078A2 (es)
EA (1) EA201791550A1 (es)
ES (1) ES2783624T3 (es)
IL (1) IL253402A0 (es)
MX (1) MX2017009145A (es)
PE (1) PE20171184A1 (es)
SG (1) SG11201705646XA (es)
TW (1) TW201632531A (es)
WO (1) WO2016115191A1 (es)
ZA (1) ZA201704738B (es)

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MX2017009145A (es) 2017-11-22
CA2973354A1 (en) 2016-07-21
US9822144B2 (en) 2017-11-21
US20160200742A1 (en) 2016-07-14
EP3245213A1 (en) 2017-11-22
US20170233436A1 (en) 2017-08-17
US20170073357A1 (en) 2017-03-16
CO2017008078A2 (es) 2017-11-10
US9676794B2 (en) 2017-06-13
ZA201704738B (en) 2019-02-27
KR20170102980A (ko) 2017-09-12
WO2016115191A1 (en) 2016-07-21
TW201632531A (zh) 2016-09-16
EA201791550A1 (ru) 2017-11-30
CN107428780B (zh) 2020-09-04
EP3245213B1 (en) 2020-03-04
BR112017014599A2 (pt) 2018-01-16
US9527871B2 (en) 2016-12-27
US20180079781A1 (en) 2018-03-22
US10112975B2 (en) 2018-10-30
SG11201705646XA (en) 2017-08-30
CL2017001824A1 (es) 2018-02-09
ES2783624T3 (es) 2020-09-17
IL253402A0 (en) 2017-09-28
JP2018503639A (ja) 2018-02-08
AU2016206798A1 (en) 2017-08-31
CN107428780A (zh) 2017-12-01
JP6498773B2 (ja) 2019-04-10

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