[go: up one dir, main page]

AR067837A1 - Conjugados de farmaco-ligando y sustratos farmaco-escindibles, composiciones que los contienen; utiles en el tratamiento de tumores y cancer - Google Patents

Conjugados de farmaco-ligando y sustratos farmaco-escindibles, composiciones que los contienen; utiles en el tratamiento de tumores y cancer

Info

Publication number
AR067837A1
AR067837A1 ARP070105968A ARP070105968A AR067837A1 AR 067837 A1 AR067837 A1 AR 067837A1 AR P070105968 A ARP070105968 A AR P070105968A AR P070105968 A ARP070105968 A AR P070105968A AR 067837 A1 AR067837 A1 AR 067837A1
Authority
AR
Argentina
Prior art keywords
substituted
unsubstituted
heteroalkyl
heterocycloalkyl
aryl
Prior art date
Application number
ARP070105968A
Other languages
English (en)
Inventor
Qian Zhang
David B Passmore
Guerlavais Bilal Sufi Vincent
Sanjeev Gangwar
Liang Chen
Original Assignee
Medarex 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 Medarex Inc filed Critical Medarex Inc
Publication of AR067837A1 publication Critical patent/AR067837A1/es

Links

Classifications

    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K47/55—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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/552—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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being an antibiotic
    • 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
    • A61K47/555—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 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
    • A61K47/556—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 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells enzyme catalyzed therapeutic agent [ECTA]
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • 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
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/59—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3 with hetero atoms directly attached in position 3
    • 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
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • 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
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • 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
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

Conjugados de fármaco-ligando y sustratos fármaco-escindibles que son citotoxinas potentes. Reivindicacion 1: Un compuesto de la formula (1) en donde L1 es un enlazador auto-inmolativo; m es un entero 0, 1, 2, 3, 4, 5 o 6; F es un enlazador que comprende la estructura (2) donde AA1 es uno o más miembros independientemente seleccionados del grupo que consiste de amino ácidos naturales y alfa-amino ácidos no naturales; c es un entero de 1 a 20; L2 es un enlazador auto-inmolativo y comprende la estructura (3) donde cada R17, R18, y R19 es seleccionado independientemente de H, alquilo sustituido, alquilo no sustituido, heteroalquilo sustituido, heteroalquilo no sustituido, arilo sustituido y arilo no sustituido, y w es un entero de 0 a 4; o es 1, L4 es un miembro enlazador, p es 0 o 1; X4 es un miembro seleccionado del grupo que consiste de grupos funcionales reactivos protegidos, grupos funcionales reactivos no protegidos, marcadores detectables, y agentes orientadores; y D comprende la estructura (4) donde el sistema de anillo A es un miembro seleccionado de un grupo arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido y grupos heterocicloalquilo sustituidos o no sustituidos, E y G son miembros independientemente seleccionados de H, alquilo sustituido o no sustituido, heteroalquilo sustituido o no sustituido, un heteroátomo, un enlace simple, o E y G se juntan para formar un sistema de anillo seleccionado de arilo sustituido o arilo no sustituido, heteroarilo sustituido o heteroarilo no sustituido, heterocicloalquilo sustituido o heterocicloalquilo no sustituido; X es un miembro seleccionado de O, S y NR23; R23 es un miembro seleccionado de H, alquilo sustituido o alquilo no sustituido, heteroalquilo sustituido o heteroalquilo no sustituido, y acilo; R3 es OR11; en donde R11 es un miembro seleccionado del grupo que consiste de H, alquilo sustituido, alquilo no sustituido, heteroalquilo sustituido, heteroalquilo no sustituido, monofosfatos, difosfatos, trifosfatos, sulfonatos, acilo, C(O)R12R13, C(O)OR12, C(O)NR12R13, P(O)(OR12)2, C(O)CHR12R13, SR12 y SiR12R13R14; en el cual R12, R13, y R14 son miembros independientemente seleccionados de H, alquilo sustituido o alquilo no sustituido, heteroalquilo sustituido o heteroalquilo no sustituido, arilo sustituido o arilo no sustituido, donde R12 y R13 juntos con el átomo de C o N al cual están enlazados son unidos opcionalmente para formar un sistema de anillo heterocicloalquil sustituido o no sustituido el cual tiene de 4 a 6 miembros, conteniendo opcionalmente 2 o más heteroátomos; R4, R4', R5 y R5' son miembros seleccionados del grupo que consiste de H, alquilo sustituido o alquilo no sustituido, arilo sustituido o arilo no sustituido, heteroarilo sustituido o heteroarilo no sustituido, heterocicloalquilo sustituido o heterocicloalquilo no sustituido, halogenos, NO2, NR15R16, NC(O)R15, OC(O)NR15R16, OC(O)OR15, C(O)R15, SR15,OR15, CR15=NR16, y O(CH2)nN(CH3)2, o cualquier par adyacente de R4, R4', R5 y R5', junto con los átomos de C a los cuales están enlazados, se enlazan para formar un sistema de anillo cicloalquil o heterocicloalquilo sustituido o no sustituido, teniendo de 4 a 6 miembros; donde n es un entero de 1 a 20; R15 y R16 son independientemente seleccionados de H, heteroalquilo sustituido o heteroalquilo no sustituido, arilo sustituido o arilo no sustituido, heteroarilo sustituido o heteroarilo no sustituido, heterocicloalquilo sustituido o heterocicloalquilo no sustituido, o peptidilo sustituido o peptidilo no sustituido, donde R15 y R16 junto con el átomo de N al cual están enlazados, rejuntan opcionalmente para formar un sistema de anillo heterocicloalquilo sustituido o heterocicloalquilo no sustituido de 4 a 6 miembros, conteniendo opcionalmente dos o más heteroátomos; R6 es un enlace simple el cual está presente o ausente y cuando los R6 y R7 presentes se juntan para formar un anillo ciclopropilo; y R7 es CH2-X1 o -CH2- unidos en dicho anillo ciclopropilo con R6, donde X1 es un grupo saliente, donde R11 enlaza dicho fármaco a L1, si está presente, o a F, o una sal farmacéuticamente aceptable del mismo.
ARP070105968A 2006-12-28 2007-12-28 Conjugados de farmaco-ligando y sustratos farmaco-escindibles, composiciones que los contienen; utiles en el tratamiento de tumores y cancer AR067837A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US88246106P 2006-12-28 2006-12-28
US99130007P 2007-11-30 2007-11-30

Publications (1)

Publication Number Publication Date
AR067837A1 true AR067837A1 (es) 2009-10-28

Family

ID=39589219

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP070105968A AR067837A1 (es) 2006-12-28 2007-12-28 Conjugados de farmaco-ligando y sustratos farmaco-escindibles, composiciones que los contienen; utiles en el tratamiento de tumores y cancer

Country Status (18)

Country Link
US (1) US8461117B2 (es)
EP (1) EP2114454A2 (es)
JP (1) JP2010522693A (es)
KR (1) KR20090098901A (es)
CN (1) CN101795711A (es)
AR (1) AR067837A1 (es)
AU (1) AU2007342052A1 (es)
BR (1) BRPI0719626A2 (es)
CA (1) CA2674055C (es)
CL (1) CL2007003849A1 (es)
EA (1) EA019962B1 (es)
IL (1) IL199416A0 (es)
MX (1) MX2009007147A (es)
NO (1) NO20092733L (es)
NZ (1) NZ578324A (es)
SG (1) SG170070A1 (es)
TW (1) TWI412367B (es)
WO (1) WO2008083312A2 (es)

Families Citing this family (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2630483C (en) 2005-12-08 2015-05-19 Medarex, Inc. Human monoclonal antibodies to o8e
TW200900059A (en) * 2007-02-21 2009-01-01 Medarex Inc Chemical linkers with single amino acids and conjugates thereof
WO2009026274A1 (en) * 2007-08-22 2009-02-26 Medarex, Inc. Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions
MX2010003581A (es) 2007-10-01 2010-08-02 Bristol Myers Squibb Co Anticuerpos humanos que se adhieren a mesotelina, y usos de los mismos.
AR069747A1 (es) * 2007-11-30 2010-02-17 Medarex Inc Conjugado anticuerpo monoclonal anti-b7h4- farmaco y metodos de utilizacion
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
WO2010062171A2 (en) 2008-11-03 2010-06-03 Syntarga B.V. Novel cc-1065 analogs and their conjugates
CN102341412B (zh) 2009-03-05 2018-01-05 梅达雷克斯有限责任公司 特异于cadm1 的全人抗体
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
JP5352742B2 (ja) 2009-08-07 2013-11-27 オームクス コーポレーション 酵素による酸化還元変化化学的脱離（ｅ−ｔｒａｃｅ）免疫学的検定法
US9250234B2 (en) 2011-01-19 2016-02-02 Ohmx Corporation Enzyme triggered redox altering chemical elimination (E-TRACE) immunoassay
DK2528625T3 (da) * 2010-04-15 2013-10-14 Spirogen Sarl Pyrrolobenzodiazepiner og konjugater deraf
LT2560645T (lt) 2010-04-21 2016-10-10 Syntarga B.V. Cc-1065 analogų ir bifunkcinių linkerių konjugatai
US8956859B1 (en) 2010-08-13 2015-02-17 Aviex Technologies Llc Compositions and methods for determining successful immunization by one or more vaccines
US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
US8852599B2 (en) * 2011-05-26 2014-10-07 Bristol-Myers Squibb Company Immunoconjugates, compositions for making them, and methods of making and use
WO2013059293A1 (en) 2011-10-17 2013-04-25 Ohmx Corporation Single, direct detection of hemoglobin a1c percentage using enzyme triggered redox altering chemical elimination (e-trace) immunoassay
US9340567B2 (en) 2011-11-04 2016-05-17 Ohmx Corporation Chemistry used in biosensors
CA2860739A1 (en) 2012-01-09 2013-07-18 Ohmx Corporation Enzyme cascade methods for e-trace assay signal amplification
SMT201700137T1 (it) 2012-02-13 2017-05-08 Bristol Myers Squibb Co Composti di endiini, loro coniugati, e loro usi e metodi
CN104519897A (zh) 2012-06-08 2015-04-15 比奥根艾迪克Ma公司 促凝血化合物
EP2863940A4 (en) 2012-06-08 2016-08-10 Biogen Ma Inc CHIMERIC COAGULATION FACTORS
AR091649A1 (es) 2012-07-02 2015-02-18 Bristol Myers Squibb Co Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos
JP2015529809A (ja) 2012-07-27 2015-10-08 オームクス コーポレイション 酵素及び他の標的分析物の存在及び活性の切断前検出後の単分子層の電気測定
EP2877592B1 (en) 2012-07-27 2016-09-21 Ohmx Corporation Electronic measurements of monolayers following homogeneous reactions of their components
US9943610B2 (en) 2012-12-21 2018-04-17 Bioalliance C.V. Hydrophilic self-immolative linkers and conjugates thereof
JP6302490B2 (ja) 2013-02-14 2018-03-28 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ツブリシン化合物、その製造および使用方法
TR201911139T4 (tr) 2013-03-15 2019-08-21 Zymeworks Inc Sitotoksik ve anti-mitotik bileşikler ve bunları kullanmanın yöntemleri.
PL2991683T3 (pl) 2013-05-02 2020-03-31 Glykos Finland Oy Koniugaty glikoproteiny lub glikanu z toksycznym ładunkiem
WO2015023355A1 (en) * 2013-08-12 2015-02-19 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
MX2016007578A (es) * 2013-12-16 2016-10-03 Genentech Inc Compuestos de conjugado anticuerpo-farmaco dimerico de 1-(clorometil)-2,3-dihidro-1h-benzo [e] indol, y metodos de uso y tratamiento.
KR102384740B1 (ko) 2013-12-27 2022-04-07 자임워크스 인코포레이티드 약물 접합체를 위한 설폰아마이드-함유 연결 시스템
ES2687225T3 (es) 2014-01-10 2018-10-24 Synthon Biopharmaceuticals B.V. Método de purificación de conjugados anticuerpo-fármaco unidos a Cys
EP3647322B1 (en) 2014-03-20 2021-10-20 Bristol-Myers Squibb Company Stabilized fibronectin based scaffold molecules
SG10201810507WA (en) 2014-06-06 2018-12-28 Bristol Myers Squibb Co Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof
MX2016016490A (es) 2014-06-20 2017-07-28 Bioalliance Cv Conjugados de farmaco-anticuerpo anti-receptor de folato alfa (fra) y metodos de uso de los mismos.
US10973920B2 (en) 2014-06-30 2021-04-13 Glykos Finland Oy Saccharide derivative of a toxic payload and antibody conjugates thereof
US20160041118A1 (en) 2014-08-11 2016-02-11 Ohmx Corporation Enzyme triggered redox altering chemical elimination (e-trace) assay with multiplexing capabilities
ES2886884T3 (es) * 2014-09-11 2021-12-21 Seagen Inc Suministro dirigido de sustancias farmacéuticas que contienen amina terciaria
CN113416229B (zh) 2014-09-17 2024-12-13 酵活英属哥伦比亚有限公司 细胞毒性和抗有丝分裂化合物、及其使用方法
CN104356048B (zh) * 2014-11-02 2016-08-24 浙江医药高等专科学校 环己烷羧酸酰胺类衍生物、其制备方法和用途
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
SI3221363T1 (sl) 2014-11-21 2020-09-30 Bristol-Myers Squibb Company Protitelesa proti CD73 in njihova uporaba
CN107250157B (zh) 2014-11-21 2021-06-29 百时美施贵宝公司 包含修饰的重链恒定区的抗体
CN107207379B (zh) 2014-11-25 2021-08-10 百时美施贵宝公司 用于生物制品的18f-放射性标记的方法和组合物
KR102632418B1 (ko) 2014-11-25 2024-01-31 브리스톨-마이어스 스큅 컴퍼니 영상화를 위한 신규 pd-l1 결합 폴리펩티드
WO2016097865A1 (en) 2014-12-19 2016-06-23 Regenesance B.V. Antibodies that bind human c6 and uses thereof
US20160178562A1 (en) 2014-12-19 2016-06-23 Ohmx Corporation Competitive enzymatic assay
US9526801B2 (en) 2015-01-14 2016-12-27 Bristol-Myers Squibb Company Heteroarylene-bridged benzodiazepine dimers, conjugates thereof, and methods of making and using
MA41374A (fr) * 2015-01-20 2017-11-28 Cytomx Therapeutics Inc Substrats clivables par métalloprotéase matricielle et clivables par sérine protéase et procédés d'utilisation de ceux-ci
EP3268048B1 (en) 2015-03-10 2019-05-08 Bristol-Myers Squibb Company Antibodies conjugatable by transglutaminase and conjugates made therefrom
JP6797137B2 (ja) 2015-05-29 2020-12-09 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｏｘ４０に対する抗体およびその使用
WO2017048728A1 (en) * 2015-09-14 2017-03-23 Rutgers, The State University Of New Jersey Targeted conjugates
WO2017053619A1 (en) 2015-09-23 2017-03-30 Bristrol-Myers Squibb Company Glypican-3binding fibronectin based scafflold molecules
US10618935B2 (en) 2015-11-03 2020-04-14 Industrial Technology Research Institute Antibody-drug conjugate (ADC) and method for forming the same
ES2926969T3 (es) 2015-11-19 2022-10-31 Bristol Myers Squibb Co Anticuerpos contra el receptor de factor de necrosis de tumor inducido por glucocorticoides (gitr) y usos de los mismos
GB2545169B (en) * 2015-12-01 2019-10-09 Ellipses Pharma Ltd Taxane Prodrug Comprising A Membrane Type Matrix Metalloproteinase Cleavage Site
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
WO2017112624A1 (en) 2015-12-21 2017-06-29 Bristol-Myers Squibb Company Variant antibodies for site-specific conjugation
RU2766000C2 (ru) 2016-01-08 2022-02-07 АльтруБио Инк. Четырехвалентные антитела к psgl-1 и их применения
KR20220033522A (ko) 2016-03-04 2022-03-16 브리스톨-마이어스 스큅 컴퍼니 항-cd73 항체와의 조합 요법
IL262396B2 (en) 2016-04-15 2023-09-01 Macrogenics Inc New b7-h3 binding molecules, drug-antibody conjugates and their uses
WO2017210335A1 (en) 2016-06-01 2017-12-07 Bristol-Myers Squibb Company Imaging methods using 18f-radiolabeled biologics
KR102397783B1 (ko) 2016-06-01 2022-05-12 브리스톨-마이어스 스큅 컴퍼니 Pd-l1 결합 폴리펩티드에 의한 pet 영상화
ES3005961T3 (en) 2016-07-14 2025-03-17 Bristol Myers Squibb Company Antibodies against tim3 and uses thereof
WO2018035391A1 (en) 2016-08-19 2018-02-22 Bristol-Myers Squibb Company Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use
US20190218294A1 (en) 2016-09-09 2019-07-18 Bristol-Myers Squibb Company Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
WO2018064094A1 (en) 2016-09-28 2018-04-05 Bristol-Myers Squibb Company Enantioselective synthesis of pyrroloindole compounds
BR112019007760A2 (pt) * 2016-10-17 2019-09-03 Pfizer anticorpos anti-edb e conjugados de anticorpo-fármaco
WO2018075842A1 (en) 2016-10-20 2018-04-26 Bristol-Myers Squibb Company Condensed benzodiazepine derivatives and conjugates made therefrom
WO2018151821A1 (en) 2017-02-17 2018-08-23 Bristol-Myers Squibb Company Antibodies to alpha-synuclein and uses thereof
WO2018208868A1 (en) 2017-05-10 2018-11-15 Smet Pharmaceutical Inc Human monoclonal antibodies against lag3 and uses thereof
WO2018218004A1 (en) 2017-05-24 2018-11-29 The Board Of Regents Of The University Of Texas System Linkers for antibody drug conjugates
MX2019013132A (es) 2017-05-25 2020-01-27 Bristol Myers Squibb Co Anticuerpos que comprenden regiones constantes pesadas modificadas.
IL308744A (en) 2017-06-20 2024-01-01 Imbria Pharmaceuticals Inc Compositions for use in increasing efficiency of cardiac metabolism
US10494370B2 (en) 2017-08-16 2019-12-03 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
US10472361B2 (en) 2017-08-16 2019-11-12 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor
US10457681B2 (en) 2017-08-16 2019-10-29 Bristol_Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor
US10487084B2 (en) 2017-08-16 2019-11-26 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor
US10508115B2 (en) 2017-08-16 2019-12-17 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
US11230601B2 (en) 2017-10-10 2022-01-25 Tilos Therapeutics, Inc. Methods of using anti-lap antibodies
JP7358361B2 (ja) 2018-01-12 2023-10-10 ブリストル－マイヤーズ スクイブ カンパニー Ｔｉｍ３に対する抗体およびその使用
CA3093407A1 (en) 2018-03-23 2019-09-26 Bristol-Myers Squibb Company Antibodies against mica and/or micb and uses thereof
KR20200139219A (ko) 2018-04-02 2020-12-11 브리스톨-마이어스 스큅 컴퍼니 항-trem-1 항체 및 이의 용도
WO2019209811A1 (en) 2018-04-24 2019-10-31 Bristol-Myers Squibb Company Macrocyclic toll-like receptor 7 (tlr7) agonists
WO2019246445A1 (en) 2018-06-20 2019-12-26 The Research Foundation For The State University Of New York Triazamacrocycle-derived chelator compositions for coordination of imaging and therapy metal ions and methods of using same
WO2020003210A1 (en) 2018-06-29 2020-01-02 Kangwon National University University-Industry Cooperation Foundation Anti-l1cam antibodies and uses thereof
US11554120B2 (en) 2018-08-03 2023-01-17 Bristol-Myers Squibb Company 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor
WO2020053255A1 (en) * 2018-09-12 2020-03-19 Technische Universität München Therapeutic and diagnostic agents for cancer
EP3849997B1 (en) 2018-09-12 2024-05-01 Technische Universität München Cxcr4-targeted diagnostic and therapeutic agents with reduced species selectivity
CN113164780A (zh) 2018-10-10 2021-07-23 泰洛斯治疗公司 抗lap抗体变体及其用途
EP3866794B1 (en) 2018-10-17 2024-12-04 Imbria Pharmaceuticals, Inc. Methods of treating rheumatic diseases using trimetazidine-based compounds
BR112021008293A2 (pt) 2018-11-09 2021-08-03 Byondis B.V. composição, método, e, método para liberar/aprovar um lote de conjugado de anticorpo-fármaco
US20220106400A1 (en) 2018-11-28 2022-04-07 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
SMT202300159T1 (it) 2018-11-30 2023-07-20 Bristol Myers Squibb Co Anticorpo comprendente un’estensione carbossiterminale della catena leggera contenente glutammina, suoi coniugati e metodi ed usi
WO2020117627A1 (en) 2018-12-03 2020-06-11 Bristol-Myers Squibb Company Anti-ido antibody and uses thereof
CA3121902A1 (en) 2018-12-04 2020-06-11 Der-Yang Tien Stereocomplexes for the delivery of anti-cancer agents
US12049505B2 (en) 2018-12-06 2024-07-30 Cytomx Therapeutics, Inc. Matrix metalloprotease-cleavable and serine or cysteine protease-cleavable substrates and methods of use thereof
US20220031860A1 (en) 2018-12-12 2022-02-03 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
CN109762067B (zh) 2019-01-17 2020-02-28 北京天广实生物技术股份有限公司 结合人Claudin 18.2的抗体及其用途
KR102570405B1 (ko) 2019-01-22 2023-08-25 브리스톨-마이어스 스큅 컴퍼니 Il-7r 알파 서브유닛에 대한 항체 및 이의 용도
CA3133311A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Extracellular vesicles for vaccine delivery
US20240108747A1 (en) 2019-03-21 2024-04-04 Lonza Sales Ag Extracellular vesicle conjugates and uses thereof
JP2022531095A (ja) 2019-04-17 2022-07-06 コディアック バイオサイエンシーズ， インコーポレイテッド エキソソーム及びａａｖの組成物
EP3963085A4 (en) * 2019-05-01 2022-09-14 The University of North Carolina at Chapel Hill Inhibitors of rna-binding proteins, compositions thereof, and therapeutic uses thereof
EP3994158A1 (en) 2019-07-03 2022-05-11 Codiak BioSciences, Inc. Extracellular vesicles targeting t cells and uses thereof
US20220332817A1 (en) 2019-07-15 2022-10-20 Bristol-Myers Squibb Company Antibodies against human trem-1 and uses thereof
WO2021011678A1 (en) 2019-07-15 2021-01-21 Bristol-Myers Squibb Company Anti-trem-1 antibodies and uses thereof
JP2022544289A (ja) 2019-08-14 2022-10-17 コディアック バイオサイエンシーズ， インコーポレイテッド Ｓｔａｔ６を標的とする細胞外小胞－ａｓｏ構築物
US20230132093A1 (en) 2019-08-14 2023-04-27 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
MX2022001769A (es) 2019-08-14 2022-06-09 Codiak Biosciences Inc Construcciones de vesícula extracelular-oligonucleótido antisentido (aso) que se dirigen a la proteína beta de unión al potenciador ccaat (cebp)/beta.
CN114641570A (zh) 2019-08-14 2022-06-17 科迪亚克生物科学公司 具有靶向kras的反义寡核苷酸的细胞外囊泡
BR112022002599A2 (pt) 2019-08-14 2022-07-19 Codiak Biosciences Inc Vesícula extracelular ligada a moléculas e usos da mesma
WO2021030768A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with stat3-antisense oligonucleotides
EP4026911A4 (en) * 2019-09-05 2023-12-13 National University Corporation Tokyo University Of Agriculture and Technology Tryptase activity measurement substrate
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
US20230057939A1 (en) 2020-01-13 2023-02-23 Neoimmunetech, Inc. Method of treating a tumor with a combination of il-7 protein and a bispecific antibody
JP2021120367A (ja) 2020-01-30 2021-08-19 エイムドバイオ株式会社 ベンゾセレノフェン系化合物、これを含む薬学的組成物及び抗体−薬物複合体
BR112022017174A2 (pt) 2020-02-27 2022-10-18 Chia Tai Tianqing Pharmaceutical Group Co Ltd Anticorpo monoclonal isolado, ou uma porção de ligação ao antígeno do mesmo, nucleotídeo, vetor de expressão, célula hospedeira, composição farmacêutica e métodos de tratamento de uma doença alérgica e de um tumor
EP4132971A1 (en) 2020-04-09 2023-02-15 Merck Sharp & Dohme LLC Affinity matured anti-lap antibodies and uses thereof
US11780811B2 (en) 2020-06-30 2023-10-10 Imbria Pharmaceuticals, Inc. Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate
US11530184B2 (en) 2020-06-30 2022-12-20 Imbria Pharmaceuticals, Inc. Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate
CN112255908B (zh) * 2020-11-16 2024-12-03 西安轻工业钟表研究所有限公司 一种指针式卫星光伏时钟
CN112553274B (zh) * 2020-12-02 2023-06-13 江南大学 大豆提取物Bowman-Birk inhibitor切割DNA的方法
CN114685669A (zh) 2020-12-30 2022-07-01 和铂医药(苏州)有限公司 结合trop2的抗体及其用途
CA3207947A1 (en) 2021-02-17 2022-08-25 Aaron Noyes Extracellular vesicle linked to a biologically active molecule via an optimized linker and an anchoring moiety
WO2022198231A1 (en) 2021-03-18 2022-09-22 Seagen Inc. Selective drug release from internalized conjugates of biologically active compounds
US20240376224A1 (en) 2021-04-02 2024-11-14 The Regents Of The University Of California Antibodies against cleaved cdcp1 and uses thereof
US11883396B2 (en) 2021-05-03 2024-01-30 Imbria Pharmaceuticals, Inc. Methods of treating kidney conditions using modified forms of trimetazidine
CA3234995A1 (en) 2021-10-14 2023-04-20 Latticon (Suzhou) Biopharmaceuticals Co., Ltd. Novel antibody-cytokine fusion protein, preparation method therefor and use thereof
CN114181216A (zh) * 2021-12-27 2022-03-15 苏州新药篮生物医药科技有限公司 一种3,6-二氢吡咯并[3,2-e]吲哚-2-甲酸甲酯的制备方法
WO2023173393A1 (zh) 2022-03-18 2023-09-21 北京天广实生物技术股份有限公司 结合b7-h3的抗体及其用途
CN116727114B (zh) * 2023-07-19 2024-07-09 昆明理工大学 一种短流程浮选回收锂云母的方法

Family Cites Families (118)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4169888A (en) 1977-10-17 1979-10-02 The Upjohn Company Composition of matter and process
US4391904A (en) 1979-12-26 1983-07-05 Syva Company Test strip kits in immunoassays and compositions therein
US4671958A (en) 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4978757A (en) 1984-02-21 1990-12-18 The Upjohn Company 1,2,8,8a-tetrahydrocyclopropa (C) pyrrolo [3,2-e)]-indol-4(5H)-ones and related compounds
US4912227A (en) 1984-02-21 1990-03-27 The Upjohn Company 1,2,8,8A-tetrahydrocyclopropa(c)pyrrolo(3,2-e)-indol-4-(5H)-ones and related compounds
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
EP0271581B1 (en) 1986-04-17 1993-01-13 Kyowa Hakko Kogyo Co., Ltd. Novel compounds dc-88a and dc-89a1 and process for their preparation
US5332837A (en) 1986-12-19 1994-07-26 The Upjohn Company CC-1065 analogs
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
US5773435A (en) 1987-08-04 1998-06-30 Bristol-Myers Squibb Company Prodrugs for β-lactamase and uses thereof
US4952394A (en) 1987-11-23 1990-08-28 Bristol-Myers Company Drug-monoclonal antibody conjugates
US4994578A (en) 1987-11-27 1991-02-19 Meiji Seika Kaisha, Ltd. Certain anti-tumor duocarmycin antibiotics from streptomyces
US5147786A (en) 1988-04-22 1992-09-15 Monsanto Company Immunoassay for the detection of α-haloacetamides
JP2642165B2 (ja) 1988-07-22 1997-08-20 協和醗酵工業株式会社 新規ｄｃ−８９化合物およびその製造法
US5084468A (en) 1988-08-11 1992-01-28 Kyowa Hakko Kogyo Co., Ltd. Dc-88a derivatives
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5176996A (en) 1988-12-20 1993-01-05 Baylor College Of Medicine Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
JP2598116B2 (ja) 1988-12-28 1997-04-09 協和醗酵工業株式会社 新規物質ｄｃ１１３
US5187186A (en) 1989-07-03 1993-02-16 Kyowa Hakko Kogyo Co., Ltd. Pyrroloindole derivatives
JP2510335B2 (ja) 1989-07-03 1996-06-26 協和醗酵工業株式会社 Ｄｃ―８８ａ誘導体
WO1991004753A1 (en) 1989-10-02 1991-04-18 Cetus Corporation Conjugates of antisense oligonucleotides and therapeutic uses thereof
US5495009A (en) 1989-10-24 1996-02-27 Gilead Sciences, Inc. Oligonucleotide analogs containing thioformacetal linkages
US5334528A (en) 1989-10-30 1994-08-02 The Regents Of The University Of California Monoclonal antibodies to cyclodiene insecticides and method for detecting the same
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1991010741A1 (en) 1990-01-12 1991-07-25 Cell Genesys, Inc. Generation of xenogeneic antibodies
JPH05508394A (ja) 1990-04-25 1993-11-25 ファルマシア・アンド・アップジョン・カンパニー 新規なｃｃ―１０６５アナログ
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
US5137877B1 (en) 1990-05-14 1996-01-30 Bristol Myers Squibb Co Bifunctional linking compounds conjugates and methods for their production
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
EP0468400B1 (en) 1990-07-26 1996-08-14 Kyowa Hakko Kogyo Co., Ltd. DC-89 derivatives as antitumoral agents
GB9017024D0 (en) 1990-08-03 1990-09-19 Erba Carlo Spa New linker for bioactive agents
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
EP0814159B1 (en) 1990-08-29 2005-07-27 GenPharm International, Inc. Transgenic mice capable of producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
DE69233782D1 (de) 1991-12-02 2010-05-20 Medical Res Council Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken
US5622929A (en) 1992-01-23 1997-04-22 Bristol-Myers Squibb Company Thioether conjugates
CA2076465C (en) 1992-03-25 2002-11-26 Ravi V. J. Chari Cell binding agent conjugates of analogues and derivatives of cc-1065
GB9314960D0 (en) 1992-07-23 1993-09-01 Zeneca Ltd Chemical compounds
JP3514490B2 (ja) 1992-08-21 2004-03-31 杏林製薬株式会社 トリフルオロメチルピロロインドールカルボン酸エステル誘導体及びその製造方法
US5288514A (en) 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US5324483B1 (en) 1992-10-08 1996-09-24 Warner Lambert Co Apparatus for multiple simultaneous synthesis
DE4314091A1 (de) 1993-04-29 1994-11-03 Boehringer Mannheim Gmbh Immunologisches Nachweisverfahren für Triazine
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US5786377A (en) 1993-11-19 1998-07-28 Universidad De Santiago De Compostela Pyrrolo 3,2-E!indol derivatives, process for the preparation thereof and applications
ATE271557T1 (de) 1994-04-22 2004-08-15 Kyowa Hakko Kogyo Kk Dc-89 derivat
JPH07309761A (ja) 1994-05-20 1995-11-28 Kyowa Hakko Kogyo Co Ltd デュオカルマイシン誘導体の安定化法
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
PT769967E (pt) 1994-08-19 2008-02-18 Univ Catholique Louvain Conjugados que compreendem um agente antitumoral e a sua utilização
WO1996010405A1 (en) 1994-09-30 1996-04-11 Kyowa Hakko Kogyo Co., Ltd. Antitumor agent
HUT77654A (hu) 1994-11-29 1998-07-28 Kyorin Pharmaceutical Co.,Ltd. Bisz[(1,2,3,6-tetrahidro-pirrolo[3,2-e]indol-3-il)-akrilamid]-származékok és eljárás előállításukra
ES2299177T3 (es) 1995-05-10 2008-05-16 Kyowa Hakko Kogyo Co., Ltd. Conjugados de citotoxinas que contienen dipeptidos.
US5686237A (en) 1995-06-05 1997-11-11 Al-Bayati; Mohammed A. S. Use of biomarkers in saliva to evaluate the toxicity of agents and the function of tissues in both biomedical and environmental applications
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
JPH11513391A (ja) 1995-10-03 1999-11-16 ザ スクリップス リサーチ インスティテュート Ｃｃ−１０６５ 及びズオカーマイシンのｃｂｉ 類縁体
DE69632989T2 (de) 1995-10-17 2005-08-25 Combichem, Inc., San Diego Matrize für die Synthese kombinatorischer Bibliotheken in Lösung
WO1997023243A1 (en) 1995-12-22 1997-07-03 Bristol-Myers Squibb Company Branched hydrazone linkers
US6143901A (en) 1996-07-31 2000-11-07 Genesoft, Inc. Complex formation between dsDNA and pyrrole imidazole polyamides
AU711974B2 (en) 1996-03-08 1999-10-28 Scripps Research Institute, The MCBI analogs of CC-1065 and the duocarmycins
US6060608A (en) 1996-05-31 2000-05-09 The Scripps Research Institute Analogs of CC-1065 and the duocarmycins
NZ334344A (en) 1996-09-12 2000-08-25 Cancer Res Campaign Tech benzo[e]indole and pyrrolo[3,2-e]indole compounds and their use as prodrugs
US6130237A (en) 1996-09-12 2000-10-10 Cancer Research Campaign Technology Limited Condensed N-aclyindoles as antitumor agents
JPH1087666A (ja) 1996-09-18 1998-04-07 Kyorin Pharmaceut Co Ltd デュオカルマイシンｓａ及びその誘導体の製造中間体と製造方法
US6759509B1 (en) 1996-11-05 2004-07-06 Bristol-Myers Squibb Company Branched peptide linkers
WO1998025900A1 (fr) 1996-12-13 1998-06-18 Shionogi & Co., Ltd. Composes presentant une activite antitumorale
EP0996458A4 (en) 1997-03-28 2001-05-02 Scripps Research Inst SANDRAMYCIN ANALOG
JP2002510968A (ja) 1997-05-07 2002-04-09 ブリストル−マイヤーズ スクイブ カンパニー 組換え抗体−酵素融合タンパク質
EP0983248B1 (en) 1997-05-22 2004-07-14 The Scripps Research Institute Analogs of duocarmycin and cc-1065
NZ503966A (en) 1997-10-14 2002-10-25 Scripps Research Inst iso -CBI and iso -CI analogs of CC-1065 and the duocarmycins
WO1999029642A1 (en) 1997-12-08 1999-06-17 The Scripps Research Institute Synthesis of cc-1065/duocarmycin analogs
JP3045706B1 (ja) 1998-09-14 2000-05-29 科学技術振興事業団 Ｄｎａの特定塩基配列をアルキル化する化合物及びその合成法
WO2000033888A2 (en) 1998-12-11 2000-06-15 Coulter Pharmaceutical, Inc. Prodrug compounds and process for preparation thereof
US7425541B2 (en) 1998-12-11 2008-09-16 Medarex, Inc. Enzyme-cleavable prodrug compounds
US6909006B1 (en) 1999-08-27 2005-06-21 Spirogen Limited Cyclopropylindole derivatives
EP1242438B1 (en) 1999-12-29 2006-11-08 Immunogen, Inc. Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use
ATE362940T1 (de) 2000-03-16 2007-06-15 Genesoft Inc Geladene verbindungen mit einer nukleinsäure- bindenden einheit sowie deren verwendungen
AU2001262974A1 (en) 2000-05-03 2001-11-12 The Scripps Research Institute Dna alkylating agent and activation thereof
JP4061819B2 (ja) 2000-05-12 2008-03-19 独立行政法人科学技術振興機構 インターストランドクロスリンク剤の合成方法
AU6685301A (en) 2000-06-14 2001-12-24 Corixa Corp Prodrug compounds with isoleucine
JP2004501875A (ja) 2000-06-14 2004-01-22 メダレックス，インコーポレイティド トリペプチドプロドラッグ化合物
AU2001286727A1 (en) 2000-08-24 2002-03-04 Coulter Pharmaceutical, Inc. Prodrugs activated by plasmin and their use in cancer chemotherapy
EP1243276A1 (en) 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
JP2002308898A (ja) * 2001-04-06 2002-10-23 Kyowa Hakko Kogyo Co Ltd 蛋白質受容体結合性環状ペプチドおよびその製造法
US7256257B2 (en) 2001-04-30 2007-08-14 Seattle Genetics, Inc. Pentapeptide compounds and uses related thereto
US6884869B2 (en) 2001-04-30 2005-04-26 Seattle Genetics, Inc. Pentapeptide compounds and uses related thereto
US20030083263A1 (en) 2001-04-30 2003-05-01 Svetlana Doronina Pentapeptide compounds and uses related thereto
US6762179B2 (en) 2001-05-31 2004-07-13 Vertex Pharmaceuticals Incorporated Thiazole compounds useful as inhibitors of protein kinase
CN101671335A (zh) * 2001-05-31 2010-03-17 梅达莱克斯公司 细胞毒素、其有用的前体药物、连接基团和稳定剂
ES2364452T3 (es) 2001-06-11 2011-09-02 Medarex, Inc. Método para diseñar compuestos profármacos activados por cd10.
EP1423110A4 (en) 2001-09-07 2005-04-27 Scripps Research Inst CBI ANALOGUE OF CC-1065 AND DUOCARMYCINES
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
US6534660B1 (en) 2002-04-05 2003-03-18 Immunogen, Inc. CC-1065 analog synthesis
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
US7776814B2 (en) 2002-07-09 2010-08-17 R&D-Biopharmaceuticals Gmbh Tubulysin conjugates
AU2003266233A1 (en) 2002-07-09 2004-01-23 Morphochem Aktiengesellschaft Fur Kombinatorische Chemie Novel tubulysin analogues
AU2003294210A1 (en) 2002-07-31 2004-05-04 Seattle Genetics, Inc Anti-cd20 antibody-drug conjugates for the treatment of cancer and immune disorders
CA2512867C (en) * 2003-01-27 2014-08-26 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
WO2004101767A2 (en) 2003-05-13 2004-11-25 The Scripps Research Institute Cbi analogues of the duocarmycins and cc-1065
JP4806680B2 (ja) * 2004-05-19 2011-11-02 メダレックス インコーポレイテッド 自己犠牲リンカー及び薬剤複合体
EP1789391B1 (en) * 2004-07-23 2017-06-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
US7714016B2 (en) * 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
AU2006294554B2 (en) * 2005-09-26 2013-03-21 E. R. Squibb & Sons, L.L.C. Antibody-drug conjugates and methods of use
WO2007059404A2 (en) * 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
JP5346589B2 (ja) 2006-02-02 2013-11-20 シンタルガ・ビーブイ 水溶性ｃｃ−１０６５類似体及びその接合体
IN2009KN02404A (es) 2006-12-14 2015-08-07 Medarex Inc
TW200900059A (en) 2007-02-21 2009-01-01 Medarex Inc Chemical linkers with single amino acids and conjugates thereof

Also Published As

Publication number Publication date
US20100145036A1 (en) 2010-06-10
CA2674055C (en) 2016-02-23
US8461117B2 (en) 2013-06-11
EA200970648A1 (ru) 2010-04-30
IL199416A0 (en) 2011-08-01
TW200833683A (en) 2008-08-16
BRPI0719626A2 (pt) 2014-06-24
WO2008083312A3 (en) 2010-01-14
EP2114454A2 (en) 2009-11-11
CA2674055A1 (en) 2008-07-10
JP2010522693A (ja) 2010-07-08
MX2009007147A (es) 2009-08-25
EA019962B1 (ru) 2014-07-30
CL2007003849A1 (es) 2008-07-04
WO2008083312A2 (en) 2008-07-10
KR20090098901A (ko) 2009-09-17
NO20092733L (no) 2009-07-20
TWI412367B (zh) 2013-10-21
AU2007342052A1 (en) 2008-07-10
CN101795711A (zh) 2010-08-04
SG170070A1 (en) 2011-04-29
NZ578324A (en) 2012-01-12

Similar Documents

Publication Publication Date Title
AR067837A1 (es) Conjugados de farmaco-ligando y sustratos farmaco-escindibles, composiciones que los contienen; utiles en el tratamiento de tumores y cancer
AR065404A1 (es) Conjugados farmaco-ligando, los que se unen a citotoxinas potentes, composicion farmaceutica que los contienen y su uso para retardar o detener el crecimiento de un tumor en un mamifero
IL263973A (en) Protein-polymer-drug couplings
JP2017518304A5 (es)
ATE507845T1 (de) Polyacetal-arzneimittelkonjugate als freisetzungssystem
IL276322B2 (en) Lipid-like nanocomplexes and uses thereof
JP2014528466A5 (es)
CY1122662T1 (el) Προϊοντα συζευξης αντισωματος φαρμακου
JP2010522693A5 (es)
BR0112104A (pt) Processos para tratamento de doenças reumáticas usando uma molécula de ctla4 solúvel
AR050425A1 (es) Antagonistas multivalentes de vla-4 que comprende fracciones polimericas. composiciones farmaceuticas
CA2499036A1 (en) 1,3,5-triazines for treatment of viral diseases
CA2653941A1 (en) Substituted amino purine derivatives and uses thereof
JP2018509394A5 (es)
BR0211228A (pt) Composto, composição farmacêutica e seus usos
EA201070163A1 (ru) Цитотоксические средства, включающие новые производные томаймицина, и их терапевтическое применение
AR061838A1 (es) Moduladores de propiedades farmacocineticas de terapeuticos
WO2006124737A3 (en) Molecular constructs suitable for targeted conjugates
AU2016279051A1 (en) Delivery systems for controlled drug release
ATE450499T1 (de) Durch enzyme spaltbare prodrugs von substituierten stickstoff-lost-derivaten
WO1998000173A3 (en) Targeted drug delivery using sulfonamide derivatives
PE20231947A1 (es) Conjugados de anticuerpo y farmaco
BR112020005605A2 (pt) novos conjugados de amanitina direcionados a psma
AR035230A1 (es) Compuestos de bencimidazol, proceso para su preparacion, composicion farmaceutica, proceso para la preparacion de dicha composicion farmaceutica, y usos de estos compuestos para la elaboracion de medicamentos
AR130181A1 (es) Compuestos citotóxicos y sus conjugados

Legal Events

Date Code Title Description
FB Suspension of granting procedure