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AR086364A1 - 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 mismos

Info

Publication number
AR086364A1
AR086364A1 ARP120101372A ARP120101372A AR086364A1 AR 086364 A1 AR086364 A1 AR 086364A1 AR P120101372 A ARP120101372 A AR P120101372A AR P120101372 A ARP120101372 A AR P120101372A AR 086364 A1 AR086364 A1 AR 086364A1
Authority
AR
Argentina
Prior art keywords
group
marks
hydroxy
methyl
point
Prior art date
Application number
ARP120101372A
Other languages
English (en)
Inventor
Kopitz Charlotte Christine Dr
Willuda Jrg Dr
Schuhmacher Joachim Dr
Linden Lars Dr
Mahlert Christoph Dr
El Sheikh Sherif Dr
Stelte-Ludwig Beatrix Dr
Simone Greven
Lerchen Hans Dr
Heisler Iring Georg-Dr
Beier Rudolf Dr
Bruder Sandra Dr
Harrenga Axel Dr
Petrul Heike Dr
Jrien Hannah Dr
Thierauch Karl Dr
Golfier Sven Heinz-Dr
Sandra Borkowski
Original Assignee
Bayer Ip Gmbh
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 Bayer Ip Gmbh filed Critical Bayer Ip Gmbh
Publication of AR086364A1 publication Critical patent/AR086364A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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Abstract

La presente solicitud se refiere a conjugados de principio activo-ligante (ADC) de N,N-dialquilauriestatinas dirigidos hacia la diana C4.4a 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. Los tratamientos de este tipo 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 representa un número de 1 a 50; AK representa un ligante; el grupo §-G-L1-B-L2-§§ representa 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 representa un resto seleccionado del grupo de fórmulas (2), en la que #3 marca el punto de unión con el átomo de nitrógeno; R1 representa hidrógeno o metilo; R2 representa 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 fórmula (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 representa un heterociclo mono- o bicíclico dado el caso sustituido seleccionado del grupo de fórmulas (4), en la que #6 marca el punto de unión con el grupo carbonilo; R6 representa hidrógeno, hidroxi o benciloxi; R3 representa hidrógeno o metilo; R4 representa 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 representa un grupo de la fórmula -C(=O)-OR7, -C(=O)-NR8R9, -C(=O)-NH-NH-R10 o -CH2-O-R11, en la que R7 representa hidrógeno, metilo, etilo, n-propilo, ter-butilo, bencilo o adamantilmetilo; R8 representa hidrógeno o metilo; R9 representa 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 representa benzoílo; R11 representa bencilo, que en el grupo fenilo puede estar sustituido con metoxicarbonilo o carboxilo; R5 representa hidrógeno, metilo o un resto del grupo de fórmulas (6), en la que #9 marca el punto de unión con -CHC(R26)-T2; R12 representa fenilo que puede estar sustituido con metoxicarbonilo, carboxilo o un grupo de la fórmula S(O)2OH; R13 representa fenilo que puede estar sustituido con metoxicarbonilo o carboxilo; R26 representa hidrógeno o hidroxi; T2 representa fenilo, bencilo, 1H-indol-3-ilo o 1H-indol-3-ilmetilo; R35 representa metilo o hidroxi; así como sus sales, solvatos y solvatos de las sales.
ARP120101372A 2011-04-21 2012-04-20 Conjugados de principio activo-ligante (adc) y el uso de los mismos AR086364A1 (es)

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EP11168558 2011-06-01
EP11168556 2011-06-01
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