AR050521A1 - Combinaciones para el tratamiento de enfermedades que implican una proliferacion celular - Google Patents

Combinaciones para el tratamiento de enfermedades que implican una proliferacion celular

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Publication number
AR050521A1
AR050521A1 ARP050103380A ARP050103380A AR050521A1 AR 050521 A1 AR050521 A1 AR 050521A1 AR P050103380 A ARP050103380 A AR P050103380A AR P050103380 A ARP050103380 A AR P050103380A AR 050521 A1 AR050521 A1 AR 050521A1
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AR
Argentina
Prior art keywords
alkyl
inhibitors
optionally
aryl
synthetic
Prior art date
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ARP050103380A
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English (en)
Inventor
Gerd Munzert
Martin Steegmaier
Anke Baum
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Boehringer Ingelheim Int
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=35241347&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR050521(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of AR050521A1 publication Critical patent/AR050521A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oncology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La presente se refiere a una composicion farmacéutica para el tratamiento de enfermedades que implican una proliferacion celular. También se refiere a un método para el tratamiento de dichas enfermedades, que comprende la co-administracion de un compuesto de formula (1), en donde los grupos L, R1, R2, R3, R4 y R5 tienen los significados dados en la reivindicaciones y en la parte descriptiva, opcionalmente en forma de sus tautomeros, racematos, enantiomeros, diastereoisomeros y sus mezclas y, opcionalmente, en forma de sus sales por adicion de ácidos, solvatos, hidratos, polimorfos, derivados fisiologicamente funcionales o profármacos farmacologicamente aceptables, y una cantidad eficaz de un compuesto activo 2 y/o co-tratamiento con terapia de radiacion, en una relacion que proporciona un efecto aditivo y sinérgico, y al uso combinado de un compuesto de formula (1) y de una cantidad eficaz de un compuesto activo 2 y/o radioterapia, para la fabricacion de preparaciones de combinacion farmacéuticas correspondientes. Combinacion farmacéutica y kit de preparacion de combinacion farmacéutica. Reivindicacion 1: Una combinacion farmacéutica, que comprende cantidad eficaces de: i) un compuesto de formula (1), en donde: R1, R2, que pueden ser idénticos o diferentes, significan hidrogeno o alquilo C1-6 opcionalmente sustituido; o R1 y R2 juntos significan un puente alquilo de 2 a 5 miembros que puede contener 1 a 2 heteroátomos; R3 significa hidrogeno o un grupo seleccionado entre alquilo C1-12, alquenilo C2-12, alquinilo C2-12 o arilo C6-14 opcionalmente sustituido; o un grupo seleccionado entre cicloalquilo C3-12, cicloalquenilo C3-12, policicloalquilo C7-12, policicloalquenilo C7-12, espirocicloalquilo C5-12, heterocicloalquilo C3-12, opcionalmente sustituido y/o puenteado, que contiene 1 a 2 heteroátomos, y heterocicloalquenilo C3-12 que contiene 1 a 2 heteroátomos; o R1 y R3, o R2 y R3 juntos significan un puente alquilo C3-4 saturado o insaturado que puede contener 1 heteroátomo; R4 significa un grupo seleccionado entre hidrogeno, -CN, hidroxi, -NR6R7 y halogeno; o un grupo seleccionado entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alquiloxi C1-5, alqueniloxi C2-5, alquiniloxi C2-5, alquiltio C1-6, alquilsulfoxo C1-6 y alquilsulfonilo C1-6, opcionalmente sustituido; L significa un enlazador seleccionado entre alquilo C2-10, alquenilo C2-10, arilo C6-14; -alquilC2-4-ariloC6-14, -arilC6-14-alquiloC1-4 opcionalmente sustituido, cicloalquilo C3-12 opcionalmente puenteado y heteroarilo que contiene 1 a 2 átomos de nitrogeno; n significa 0 o 1; m significa 1 o 2; R5 significa un grupo seleccionado entre morfolinilo, piperidinilo, piperazinilo, piperazinilcarbonilo, pirrolidinilo, tropenilo, R8-dicetometilpiperazinilo, sulfoxomorfolinilo, sulfonilmorfolinilo, tiomorfolinilo, -NR8R9 y azacicloheptilo opcionalmente sustituido; R6, R7, que pueden ser idénticos o diferentes, significan hidrogeno o alquilo C1-4; y R8, R9 significan sustituyentes hidrogeno no sustituidos en R5 que pueden ser idénticos o diferentes, significan hidrogeno o un grupo seleccionado entre alquilo C1-6, -alquilC1-4-cicloalquilo-C3-10, cicloalquilo C3-10, arilo C6-14, -alquilC1-4-ariloC6-14, piranilo, piridinilo, pirimidinilo, alquiloxiC1-4-carbonilo, arilC6-14-carbonilo, alquilC1-4-carbonilo, arilC6-14-metiloxicarbonilo, arilC6-14-sulfonilo, alquilC1-4-sulfonilo y -arilC6-14-alquilC1-4-sulfonilo; opcionalmente en forma de sus tautomeros racematos, enantiomeros, diastereoisomeros y sus mezclas y opcionalmente en forma de sus sales por adicion de ácidos, solvatos, hidratos, polimorfos, derivados fisiologicamente funcionales o profármacos farmacologicamente aceptables; y ii) al menos un agente 2 quimioterapéutico o terapéutico que se produce en la naturaleza, semi-sintético o sintético adicional; opcionalmente en combinacion con uno o más excipientes farmacéuticamente aceptables, y opcionalmente destinado a un co-tratamiento con radioterapia o radio-inmunoterapia en forma de un preparado combinado para uso simultáneo, separado o secuencial en el tratamiento de enfermedades que implican una proliferacion celular, migracion o apoptosis de células cancerígenas. Reivindicacion 3: Una composicion farmacéutica de acuerdo con la reivindicacion 1 o 2, en donde el agente 2 quimioterapéutico o terapéutico que se produce en la naturaleza, semi-sintético o sintético adicional se selecciona del grupo que consiste en antagonistas del receptor de VEGF de moléculas pequenas sintéticos, antagonistas del receptor del factor de crecimiento de moléculas pequenas, inhibidores del receptor de EGF y/o del receptor de VEGF y/o de receptores de integrina o cuales quiera otros receptores de la proteína tirosina quinasa que no se clasifican bajo las moléculas pequenas sintéticas, inhibidores dirigidos al receptor de EGF y/o al receptor de VEGF y/o a receptores de integrina o cualquiera otros receptores de la proteína de tirosina quinasa, que son proteínas de fusion, compuestos que interactuan con ácidos nucleicos y que se clasifican como agentes alquilantes o compuestos de platino, compuestos que interactuan con ácidos nucleicos y que se clasifican como antraciclinas, como intercaladores de ADN o como agentes reticulantes de ADN, incluidos compuestos de union de ranura pequena de ADN, anti-metabolitos, antibioticos del tipo bleomicina que se producen en la naturaleza, semi-sintéticos o sintéticos, inhibidores de enzimas transcriptoras de ADN y, especialmente, los inhibidores de topoisomerasa I o topoisomerasa II, agentes modificadores de cromatina, inhibidores de la mitosis, agentes anti-mitoticos, inhibidores del ciclo celular, inhibidores de proteasoma, enzimas, hormonas, antagonistas de hormonas, inhibidores de hormonas, inhibidores de la biosíntesis de esteroides, esteroides, citoquinas, citotoxinas selectivas de la hipoxia, inhibidores de citoquinas, linfoquinas, anticuerpos dirigidos contra citoquinas, agentes de induccion de la tolerancia oral y parenteral, agentes de soporte, sensibilizadores y protectores de la radiacion química, fármacos fotoquímicamente activados, polinucleotidos u oligonucléotidos sintéticos, fármacos antiinflamatorios no esteroides, opcionalmente modificados o conjugados, antibioticos citotoxicos, anticuerpos dirigidos contra factores de crecimiento o sus receptores, anticuerpos dirigidos contra las moléculas de la superficie de células cancerígenas, inhibidores de metaloproteinasas, metales, inhibidores de oncogenes, inhibidores de la transcripcion génica o de la traduccion de ARN o de la expresion de proteínas, complejos de elementos de tierras raras, compuestos que reducen el transporte de hialuronano mediado por uno o más transportadores ABC y agentes foto-quimioterapéuticos.
ARP050103380A 2004-08-14 2005-08-12 Combinaciones para el tratamiento de enfermedades que implican una proliferacion celular AR050521A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP04019361 2004-08-14
EP04019448 2004-08-17

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AR050521A1 true AR050521A1 (es) 2006-11-01

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US (3) US20060058311A1 (es)
EP (2) EP2275107B1 (es)
JP (1) JP5043660B2 (es)
KR (1) KR101258426B1 (es)
CN (1) CN101039673B (es)
AR (1) AR050521A1 (es)
AT (1) ATE512663T1 (es)
AU (1) AU2005274384B2 (es)
BR (1) BRPI0514357A (es)
CA (1) CA2576269C (es)
CY (1) CY1112200T1 (es)
DK (2) DK1827441T3 (es)
ES (1) ES2602465T3 (es)
HR (1) HRP20110578T1 (es)
HU (1) HUE032436T2 (es)
IL (1) IL181305A (es)
ME (1) ME01209B (es)
MX (2) MX2007001853A (es)
NZ (1) NZ553729A (es)
PL (2) PL2275107T3 (es)
PT (1) PT1827441E (es)
RS (1) RS51807B (es)
RU (2) RU2407532C9 (es)
SI (1) SI1827441T1 (es)
TW (2) TW201201810A (es)
WO (1) WO2006018182A1 (es)

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CN101039673B (zh) 2013-10-16
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