AR065404A1 - 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 - Google Patents
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 mamiferoInfo
- Publication number
- AR065404A1 AR065404A1 ARP080100692A ARP080100692A AR065404A1 AR 065404 A1 AR065404 A1 AR 065404A1 AR P080100692 A ARP080100692 A AR P080100692A AR P080100692 A ARP080100692 A AR P080100692A AR 065404 A1 AR065404 A1 AR 065404A1
- Authority
- AR
- Argentina
- Prior art keywords
- substituted
- unsubstituted
- heteroalkyl
- heterocycloalkyl
- alkyl
- Prior art date
Links
Classifications
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- 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
- C07D405/14—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 three or more hetero rings
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- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
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- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/13—Labelling of peptides
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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
La presente divulgacion provee conjugados fármaco-ligando que son potentes citotoxinas e incluyen un enlazante entre el fármaco y el ligando, en los cuales el enlazante es un unico aminoácido. La divulgacion también está dirigida a composiciones quecontienen los conjugados fármaco-ligando, y a métodos de tratamiento que los emplean. Reivindicacion 1: Un compuesto de la formula (1) en el cual L1 es un grupo alquilo sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilosustituido o no sustituido o heteroalquilo sustituido o no sustituido; m es un entero 0, 1, 2, 3, 4, 5, o 6; AA1 es un aminoácido seleccionado desde el grupo que consiste en aminoácidos naturales y alfa-aminoácidos no naturales; L2 es alquilosustituido, alquilo no sustituido, heteroalquilo sustituido, heteroalquilo no sustituido, heterocicloalquilo no sustituido, heterocicloalquilo sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido; L3 es alquilosustituido o no sustituido, heteroalquilo sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido, o heterocicloalquilo sustituido o no sustituido; o es 0 o 1; L4 es un miembro enlazante; p es 0 o 1; X4es un miembro seleccionado desde el grupo que consiste en grupos funcionales reactivos protegidos, grupos funcionales reactivos no protegidos, marcadores detectables, y agentes de direccion; y D comprende une estructura (2) en la cual es sistemaanular A es arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido o heterocicloalquilo sustituido o no sustituido; E y G son miembros seleccionados de manera independiente de entre H, alquilo sustituido o no sustituido,heteroalquilo sustituido o no sustituido, un heteroátomo, y un enlace simple, o E y G están unidos entre si para formar un sistema anular seleccionado de entre arilo sustituido y no sustituido, heteroarilo sustituido y no sustituido yheterocicloalquilo sustituido y no sustituido; X es un miembro seleccionado de entre O, S y NR23; R23 es H, alquilo sustituido o no sustituido, heteroalquilo sustituido o no sustituido o acilo; R3 es OR11, en donde R11 es H, alquilo sustituido,alquilo no sustituido, heteroalquilo sustituido, heteroalquilo no sustituido, difosfato, trifosfato, acilo, C(O)R12R13, , C(O)OR12. C(O)NR12R13, P(O)(OR12)2, C(O)CHR12R13, SR12, o SiR12R13R14, en donde R12, R13 y R14 son miembros seleccionados demanera independiente de entre H, alquilo sustituido o no sustituido, heteroalquilo sustituido y no sustituido y arilo sustituido y no sustituido, en donde R12 y R13 en conjunto con el átomo de nitrogeno o de carbono al cual están unidos estánopcionalmente unidos entre sí para formar un sistema anular heteroalquilo sustituido o no sustituido que tiene de 4 a 6 miembros, que opcionalmente contiene dos o más heteroátomos; R4, R4', R5 y R5' son miembros seleccionados de manera independientedesde el grupo que consiste en H, alquilo sustituido, alquilo no sustituido, arilo sustituido, arilo no sustituido, heteroarilo sustituido, heteroarilo no sustituido, heterocicloalquilo sustituido, heterocicloalquilo no sustituido, halogeno NO2,SO3, SO2R15, NR15R16, NR16C(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'm R5 y R5'm, en conjunto con los átomos de carbono a los cuales ellos están unidos, están unidos entresí para formar un sistema anular cicloalquilo sustituido o no sustituido o heterocicloalquilo que tiene de 4 a 6 miembros; en el cual n es un entero desde 1 hasta 20; R15 y R16 son seleccionados de manera independiente de entre H, alquilo sustituidoo no sustituido, heteroalquilo sustituido o no sustituido, arilo, sustituido o no sustituido, heteroarilo sustituido y no sustituido, heterocicloalquilo sustituido y no sustituido, y peptidilo sustituido y no sustituido, ene. cual R15 y R16 enconjunto con el átomo de nitrogeno al cual están unidos están opcionalmente unidos entre si para formar un sistema anular heterocicloalquilo sustituido o no sustituido que tiene de 4 a 6 miembros, que opcionalmente contiene dos o más heteroátomos;R6 es un enlace simple que ya sea está presente o ausente y cuando está presente R6 y R7 están unidos entre sí para formar un anillo ciclopropilo; y R7 es CH2-X1 o -CH2- unido en dicho anillo ciclopropilo con R6, en el cual X1 es un grupo saliente,en el cual al menos uno de entre R4, R4', R5 y R5', R11, R12, R13, R15 o R16 enlaza D con el resto del compuesto; o una sal farmacéuticamente aceptable del mismo.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89102807P | 2007-02-21 | 2007-02-21 |
Publications (1)
Publication Number | Publication Date |
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AR065404A1 true AR065404A1 (es) | 2009-06-03 |
Family
ID=39636949
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP080100692A AR065404A1 (es) | 2007-02-21 | 2008-02-20 | 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 |
Country Status (12)
Country | Link |
---|---|
US (1) | US8664407B2 (es) |
EP (1) | EP2121667B1 (es) |
JP (1) | JP2010519310A (es) |
KR (1) | KR20090122439A (es) |
CN (1) | CN101616911A (es) |
AR (1) | AR065404A1 (es) |
AU (1) | AU2008218766A1 (es) |
CA (1) | CA2678514A1 (es) |
CL (1) | CL2008000510A1 (es) |
IL (1) | IL200113A0 (es) |
TW (1) | TW200900059A (es) |
WO (1) | WO2008103693A2 (es) |
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WO2008103693A3 (en) | 2008-12-11 |
CA2678514A1 (en) | 2008-08-28 |
JP2010519310A (ja) | 2010-06-03 |
IL200113A0 (en) | 2010-04-15 |
CN101616911A (zh) | 2009-12-30 |
US8664407B2 (en) | 2014-03-04 |
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US20100113476A1 (en) | 2010-05-06 |
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