AR081934A1 - Compuestos de triazolopiridinas sustituidas, una combinacion farmaceutica que los comprende y el uso de dichos compuestos en la preparacion de medicamentos - Google Patents

Compuestos de triazolopiridinas sustituidas, una combinacion farmaceutica que los comprende y el uso de dichos compuestos en la preparacion de medicamentos

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Publication number
AR081934A1
AR081934A1 ARP110102073A ARP110102073A AR081934A1 AR 081934 A1 AR081934 A1 AR 081934A1 AR P110102073 A ARP110102073 A AR P110102073A AR P110102073 A ARP110102073 A AR P110102073A AR 081934 A1 AR081934 A1 AR 081934A1
Authority
AR
Argentina
Prior art keywords
alkyl
alkoxy
halo
nr8r7
hydroxy
Prior art date
Application number
ARP110102073A
Other languages
English (en)
Inventor
Hartmut Schirok
Benjamin Bader
Philip Lienau
Antje Margret Wengner
Hans Briem
Simon Holton
Gerhard Siemeister
Stefan Prechtl
Dirk Kosemund
Volker Schulze
Marcus Koppitz
Detlef Stockigt
Olaf Prien
Original Assignee
Bayer Schering Pharma Ag
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44259707&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR081934(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Schering Pharma Ag filed Critical Bayer Schering Pharma Ag
Publication of AR081934A1 publication Critical patent/AR081934A1/es

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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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Abstract

Los compuestos de la presente son útiles para el tratamiento de trastornos proliferativos tales como tumores sólidos, sarcomas, leucemias y tumores malignos linfáticos.Reivindicación 1: Un compuesto caracterizado porque es de fórmula general (1) en donde: R1 representa un grupo arilo o heteroarilo, que está sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente seleccionado entre: R6-(alquil C1-6)-, R6(CH2)n(CHOH)(CH2)m, R6-(alcoxi C1-6)-, R6-(CH2)n(CHOH)(CH2)p-O-, R6-(alcoxi C1-6-alquil C1-6)-, R6-(alcoxi C1-6-alquil C1-6)-O-, R6-O-, -C(=O)R6, -C(=O)O-R6, -OC(=O)-R6, -N(H)C(=O)R6, -N(R7)C(=O)R6, -N(H)C(=O)NR6R7, -N(R7)C(=O)NR6R7, -NR6R7, -C(=O)N(H)R6, -C(=O)NR6R7, R6-S-, R6-S(=O)-, R6-S(=O)2-, -N(H)S(=O)R6, -N(R7)S(=O)R6, -S(=O)N(H)R6, -S(=O)NR6R7, -N(H)S(=O)2R6, -N(R7)S(=O)2R6, -S(=O)2N(H)R6, -S(=O)2NR6R7, -S(=O) (=NR6)R7, -S(=O)(=NR7)R6, -N=S(=O)(R6)R7; y que está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente Rxy seleccionado entre: halo-, hidroxilo-, ciano-, nitro-, alquilo C1-6-, haloalquilo C1-6-, alcoxi C1-6-, haloalcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6- ,R8-(alquil C1-6)-, R8-(CH2)n(CHOH)(CH2)m-, R8-(alcoxi C1-6)-, R8-(CH2)n(CHOH)(CH2)p-O-, R8-(alcoxi C1-6-alquil C1-6)-, R8-(alcoxi C1-6-alquil C1-6)-O-, R8-O-, -C(=O)R8, -C(=O)O-R8, -OC(=O)-R8, -N(H)C(=O)R8, -N(R7)C(=O)R8, -N(H)C(=O)NR8R7, -N(R7)C(=O)NR8R7, -NR8R7, -C(=O)N(H)R8, -C(=O)NR8R7, R8-S-, R8-S(=O)-, R8-S(=O)2-, -N(H)S(O)R8, -N(R7)S(=O)R8, -S(=O)N(H)R8, -S(=O)NR8R7, -N(H)S(=O)2R8, -N(R7)S(=O)2R8, -S(=O)2N(H)R8, -S(=O)2NR8R7, -S(=O)(=NR8)R7, -S(=O)(=NR7)R8, -N=S(=O)(R8)R7; R2 representa un grupo arilo o heteroarilo, que está sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente seleccionado entre: R9-, R9-(alquil C1-6)-, R9-(CH2)n(CHOH)(CH2)m-, R9-(alcoxi C1-6)-, R9-(CH2)n(CHOH)(CH2)p-O-, R9-(alcoxi C1-6-alquil C1-6)-, R9-(alcoxi C1-6-alquil C1-6)-O-, -O-(CH2)n-C(=O)NR9R7, R9-O-, -C(=O)R9, -C(=O)O-R9, -OC(=O)-R9, -N(H)C(=O)R9, -N(R7)C(=O)R9, -N(H)C(=O)NR9R7, -N(R7)C(=O)NR9R7, -NR9R7, -C(=O)N(H)R9, -C(=O)NR9R7, R9-S-, R9-S(=O)-, R9-S(=O)2-, -N(H)S(=O)R9, -N(R7)S(=O)R9, -S(=O)N(H)R9, -S(=O)NR9R7, -N(H)S(=O)2R9, -N(R7)S(=O)2R9, -S(=O)2N(H)R9, -S(=O)2NR9R7, -S(=O)(=NR9)R7, -S(=O)(=NR7)R9, -N=S(=O)(R9)R7; y que está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente seleccionado entre: halo-, hidroxilo-, ciano-, nitro-, alquilo C1-6-, halo-alquilo C1-6-, alcoxi C1-6-, halo-alcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6-, R8-(alquil C1-6)-, R8-(CH2)n(CHOH)(CH2)m-, R8-(alcoxi C1-6)-, R8-(CH2)n(CHOH)(CH2)p-O-, R8-(alcoxi C1-6-alquil C1-6)-, R8-(alcoxi C1-6-alquil C1-6)-O-, -O-(CH2)n-C(=O)NR8R7, R8-O-, -C(=O)R8, -C(=O)O-R8, -OC(=O)-R8, -N(H)C(=O)R8, -N(R7)C(=O)R8, -N(H)C(=O)NR8R7, -N(R7)C(=O)NR8R7, -NR8R7, -C(=O)N(H)R8, -C(=O)NR8R7, R8-S-, R8-S(=O)-, R8-S(=O)2-, -N(H)S(=O)R8, -N(R7)S(=O)R8, -S(=O)N(H)R8, -S(=O)NR8R7, -N(H)S(=O)2R8, -N(R7)S(=O)2R8, -S(=O)2N(H)R8, -S(=O)2NR8R7, -S(=O)(=NR8)R7, -S(=O)(=NR7)R8, -N=S(=O)(R8)R7; R3 representa un átomo de hidrógeno, un átomo de halógeno, un grupo hidroxi-, amino, ciano-, nitro-, alquilo C1-4-, halo-alquilo C1-4-, alcoxi C1-4-, halo-alcoxi C1-4-, hidroxi-alquilo C1-4, alcoxi C1-4-alquilo C1-4-, halo-alcoxi C1-4-alquilo C1-4-, alquenilo C2-6-, alquinilo C2-6-, halo-alquenilo C2-6-, halo-alquinilo C2-6-, cicloalquilo C3-6-, o halo-cicloalquilo C3-6-; R4 representa un átomo de hidrógeno, un átomo de halógeno, un grupo hidroxi-, amino, ciano-, nitro-, alquilo C1-4-, halo-alquilo C1-4-, alcoxi C1-4-, halo-alcoxi C1-4-, hidroxi-alquilo C1-4, alcoxi C1-4-alquilo C1-4-, halo-alcoxi C1-4-alquilo C1-4-, alquenilo C2-6-, alquinilo C2-6-, halo-alquenilo C2-6-, halo-alquinilo C2-6-, cicloalquilo C3-6-, o halo-cicloalquilo C3-6-; R5 representa un átomo de hidrógeno; R6 representa un grupo seleccionado entre: cicloalquilo C3-6-, heterocicloalquilo- de entre 3 y 10 miembros, arilo-, heteroarilo-, -(CH2)q(cicloalquilo C3-6), -(CH2)q-(heterocicloalquilo de entre 3 y 10 miembros), -(CH2)q-arilo, o -(CH2)q-heteroarilo; donde dicho grupo está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente seleccionado entre: halo-, hidroxilo-, ciano-, nitro-, alquilo C1-6-, halo-alquilo C1-6-, alcoxi C1-6-, halo-alcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6-, R8-(alquil C1-6)-, R8-(CH2)n(CHOH)(CH2)m, R8-(alcoxi C1-6)-, R8-(CH2)n(CHOH)(CH2)p-O-, R8-(alcoxi C1-6-alquil C1-6)-, R8-(alcoxi C1-6-alquil C1-6)-O-, arilo-, R8-O-, -C(=O)R8, -C(=O)O-R8, -OC(=O)-R8, -N(H)C(=O)R8, -N(R7)C(=O)R8, -N(H)C(=O)NR8R7, -N(R7)C(=O)NR8R7, -NR8R7, -C(=O)N(H)R8, -C(=O)NR8R7, R8-S-, R8-S(=O)-, R8-S(=O)2-, -N(H)S(=O)R8, -N(R7)S(=O)R8, -S(=O)N(H)R8, -S(=O)NR8R7, -N(H)S(=O)2R8, -N(R7)S(=O)2R8, -S(=O)2N(H)R8, -S(=O)2NR8R7, -S(=O)(=NR8)R7, -S(=O)(=NR7)R8, -N=S(=O)(R8)R7; R7 representa un átomo de hidrógeno, un grupo alquilo C1-6-, o cicloalquilo C3-6-; o R6 y R7, junto con el átomo de nitrógeno al cual están unidos, representan un grupo heterocicloalquilo- de entre 3 y 10 miembros, que está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con halógeno, hidroxi, ciano-, nitro-, alquilo C1-6-, halo-alquilo C1-6-, alcoxi C1-6-, halo-alcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6-, alquenilo C2-6-, alquinilo C2-6- o cicloalquilo C3-6-; R8 representa un átomo de hidrógeno o un grupo alquilo C1-6-; R9 representa un grupo seleccionado entre: cicloalquilo C7-10-, heterocicloalquilo- de entre 3 y 10 miembros, arilo-, heteroarilo-; donde dicho grupo está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con un sustituyente seleccionado entre: halo-, hidroxilo-, ciano-, nitro-, alquilo C1-6-, halo-alquilo C1-6-, alcoxi C1-6-, halo-alcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6-, -(CH2)q-(cicloalquilo C3-6), R8-(CH2)n(CHOH)(CH2)m-, R8-(alcoxi C1-6)-, R8-(CH2)n(CHOH)(CH2)p-O-, R8-(alcoxi C1-6-alquil C1-6)-, R8-(alcoxi C1-6-alquil C1-6)-O-, arilo-, R8-O-, -C(=O)R8, -C(=O)O-R8, -OC(=O)-R8, -N(H)C(=O)R8, -N(R7)C(=O)R8, -N(H)C(=O)NR8R7, -N(R7)C(=O)NR8R7, -NR8R7, -C(=O)N(H)R8, -C(=O)NR8R7, R8-S-, R8-S(=O)-, R8-S(=O)2-, -N(H)S(=O)R8, -N(R7)S(=O)R8, -S(=O)N(H)R8, -S(=O)NR8R7, -N(H)S(=O)2R8, -N(R7)S(=O)2R8, -S(=O)2N(H)R8, -S(=O)2NR8R7, -S(=O)(=NR8)R7, -S(=O)(=NR7)R8, -N=S(=O)(R8)R7; o R9 y R7, junto con el átomo de nitrógeno al cual están unidos, representan un grupo heterocicloalquilo- de entre 3 y 10 miembros, que está opcionalmente sustituido, una o más veces, en forma idéntica o diferente, con halógeno, hidroxi, ciano-, nitro-, alquilo C1-6-, halo-alquilo C1-6-, alcoxi C1-6-, halo-alcoxi C1-6-, hidroxi-alquilo C1-6-, alcoxi C1-6-alquilo C1-6-, halo-alcoxi C1-6-alquilo C1-6-, alquenilo C2-6-, alquinilo C2-6-, -C(=O)O-R8 o cicloalquilo C3-6-; n, m, p representan, en forma independiente entre sí, el entero 0, 1, 2, 3, 4, ó 5; q representa el entero 0, 1, 2 ó 3; o un estereoisómero, un tautómero, un N-óxido, un hidrato, un solvato o una sal del mismo, o una mezcla de los mismos.
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