AR086363A1 - Conjugados de principio activo-ligante (adc) y el uso de los mismos - Google Patents
Conjugados de principio activo-ligante (adc) y el uso de los mismosInfo
- Publication number
- AR086363A1 AR086363A1 ARP120101371A ARP120101371A AR086363A1 AR 086363 A1 AR086363 A1 AR 086363A1 AR P120101371 A ARP120101371 A AR P120101371A AR P120101371 A ARP120101371 A AR P120101371A AR 086363 A1 AR086363 A1 AR 086363A1
- Authority
- AR
- Argentina
- Prior art keywords
- group
- marks
- hydrogen
- hydroxy
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
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- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- A61K31/4025—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 not condensed and containing further heterocyclic rings, e.g. cromakalim
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- 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
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- 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
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- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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Abstract
Dirigidos contra la mesotelina blanco de metabolitos efectivos de estos ADC, procedimientos para la preparación de estos ADC, el uso de estos ADC para el tratamiento y/o la prevención de enfermedades así como el uso de estos ADC para la preparación de medicamentos para el tratamiento y/o la prevención de enfermedades, especialmente de enfermedades hiperproliferativas y/o angiogénicas como por ejemplo cáncer. Tales tratamientos pueden efectuarse como monoterapias o también en combinación con otros medicamentos u otras medidas terapéuticas.Reivindicación 1: Conjugados de principio activo-ligante de la fórmula general (1), en la que: n es un número de 1 a 50; AK es un ligante; el grupo §-G-L1-B-L2-§§ es un adaptador, en la que § marca el punto de unión con el grupo AK y §§ marca el punto de unión con el átomo de nitrógeno; D es un resto seleccionado del grupo de fórmulas (2), en la que #3 marca el punto de unión con el átomo de nitrógeno; R1 es hidrógeno o metilo; R2 es isopropilo, isobutilo, sec-butilo, ter-butilo, fenilo, bencilo, 1-hidroxietilo, 4-hidroxibencilo, 4-hidroxi-3-nitrobencilo, 4-hidroxi-3-aminobencilo, 1-feniletilo, difenilmetilo, 1H-imidazol-4-ilmetilo o 1H-indol-3-ilmetilo; o R1 y R2 junto con el átomo de carbono al que están unidos forman un grupo (1S,2R)-2-fenilciclopropan-1,1-diilo de la formula (3), en la que #4 marca el punto de unión con el átomo de nitrógeno adyacente; #5 marca el punto de unión con el grupo carbonilo; el anillo A con el grupo N-O contenido en el mismo es un heterociclo mono- o bicíclico opcionalmente sustituido seleccionado del grupo de fórmulas (4), en la que #6 marca el punto de unión con el grupo carbonilo; R6 es hidrógeno, hidroxi o benciloxi; R3 es hidrógeno o metilo; R4 es isopropilo, isobutilo, sec-butilo, ter-butilo, fenilo, bencilo, 1-hidroxietilo, 4-hidroxibencilo, 4-hidroxi-3-nitrobencilo, 4-hidroxi-3-aminobencilo, 1-feniletilo, difenilmetilo, 1H-imidazol-4-ilmetilo o 1H-indol-3-ilmetilo; o R3 y R4 junto con el átomo de carbono al que están unidos forman un grupo (1S,2R)-2-fenilciclopropan-1,1-diilo de la fórmula (5), en la que #7 marca el punto de unión con el átomo de nitrógeno adyacente; #8 marca el punto de unión con el grupo T1; T1 es un grupo de la fórmula -C(=O)-OR7, -C(=O)-NR8R9, -C(=O)-NH-NH-R10 o -CH2-O-R11, en la que R7 es hidrógeno, metilo, etilo, n-propilo, ter-butilo, bencilo o adamantilmetilo; R8 es hidrógeno o metilo; R9 es hidrógeno, metilo, etilo, n-propilo o bencilo; o R8 y R9 forman junto con el átomo de nitrógeno al que están unidos un heterociclo de 4 a 7 miembros; R10 es benzoilo; R11 es bencilo, que en el grupo fenilo puede estar sustituido con metoxicarbonilo o carboxilo; R5 es hidrógeno, metilo o un resto seleccionado del grupo de fórmulas (6), en la que #9 marca el punto de unión con -CHC(R26)-T2; -R12 es fenilo que puede estar sustituido con metoxicarbonilo, carboxilo o un grupo de la fórmula -S(O)2OH; R13 es fenilo que puede estar sustituido con metoxicarbonilo o carboxilo; R26 es hidrógeno o hidroxi; T2 es fenilo, bencilo, 1H-indol-3-ilo o 1H-indol-3-ilmetilo; R35 es metilo o hidroxi; así como sus sales, solvatos y solvatos de las sales. Reivindicación 42: Anticuerpos o los fragmentos de anticuerpo que enlazan un antígeno que se enlazan con mesotelina, comprendiendo la secuencia de anticuerpos la secuencia de aminoácidos de la cadena variable pesada reproducida por la secuencia SEC ID Nº 404 y secuencia de aminoácidos de la cadena variable ligera reproducida por la secuencia SEC ID Nº 405.
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ARP120101372A Pending AR086364A1 (es) | 2011-04-21 | 2012-04-20 | Conjugados de principio activo-ligante (adc) y el uso de los mismos |
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