AR040995A1 - Terapia de combinacion para enfermedades hiperproliferativas - Google Patents

Terapia de combinacion para enfermedades hiperproliferativas

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AR040995A1
AR040995A1 ARP030102971A ARP030102971A AR040995A1 AR 040995 A1 AR040995 A1 AR 040995A1 AR P030102971 A ARP030102971 A AR P030102971A AR P030102971 A ARP030102971 A AR P030102971A AR 040995 A1 AR040995 A1 AR 040995A1
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Pfizer Prod Inc
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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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/435—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Abstract

Método para tratar enfermedades hiperproliferativas. Más particularmente, el presente se refiere a un método para tratar enfermedades hiperproliferativas, tales como el cáncer, que comprende la operación de administrar a un mamífero que necesita dicho tratamiento, sea simultánea, o sucesivamente, (i) una cantidad terapéuticamente eficaz de un derivado de taxano, un complejo de coordinación de platino seleccionado del grupo que consiste en carboplatino, tetraplatino, y topotecán, un compuesto análogo a nucleósido seleccionado del grupo que consiste en hidrocloruro de gencitabina y 5-FU, una antraciclina, un inhibidor de topoisomerasas seleccionado del grupo que consiste en etopósido, tenipósido, ancacrina, topotecán y Camptosar(R), un inhibidor de aromatasa; y (ii) una cantidad terapéuticamente eficaz de un derivado de isotiazol. Las combinaciones del presente pueden incluir opcionalmente un agente antihipertensivo. Este presente se refiere también a composiciones farmacéuticas útiles en el tratamiento de enfermedades hiperproliferativas en mamíferos, que contienen tales combinaciones. El presente también se refiere a sistemas que tienen un primer comportamiento con un compuesto de fórmula (1), y un segundo compartimento que contiene un derivado de taxano, un complejo de coordinación de platino, un compuesto análogo a nucleósido, una antraciclina, de topoisomerasas o un inhibidor de aromatasa, y un tercer compartimento que contiene un agente antihipertensivo. Reivindicación 1: Un método para tratar un trastorno hiperproliferativo en un mamífero, caracterizado porque comprende administrar a dicho mamífero que necesita dicho tratamiento, sea simultáneamente o sucesivamente, (i) una cantidad terapéuticamente eficaz de un derivado de taxano, un complejo de coordinación de platino seleccionado del grupo que consiste en carboplatino, tetraplatino y topotecán, un compuesto análogo a nucleósido seleccionado del grupo que consiste en hidrocloruro de gencitabina y 5-FU, un antraciclina, un inhibidor de topoisomeras seleccionado del grupo que consiste en etopósido, tenipósido, ansacrina, topotecán y Camptosar(R), y un inhibidor de aromatasa; y (ii) una cantidad terapéuticamente eficaz de un compuesto de fórmula (1) o una sal, profármaco o solvato farmacéuticamente aceptable del mismo, fórmula en que : X1 es O o S; R1 es H, alquilo C1-10, alquenilo C2-10, alquinilo C2-10, -C(O)(alquilo C1-10), -(CH2)t(arilo C6-10), -(CH2)t(heterociclo de 4-10 miembros), -C(O)(CH2)t(arilo C6-10) o -C(O)(CH2)(heterociclo de 5-10 miembros), en los que t es un número entero de 0 a 5; grupo alquilo que incluye opcionalmente 1 ó 2 heterorrestos seleccionados entre O, S y -N(R6)- con la condición de que dos átomos de O, dos átomos de S o un átomo de O y un átomo de S no estén directamente unidos entre sí; grupos R1 arílico y heterocíclico que están opcionalmente fusionados con un grupo arilo C6-10, un grupo cíclico saturado C5-8 o un grupo heterocíclico de 5-10 miembros; estando 1 ó 2 átomos de carbono de los restos heterocíclicos precedentes opcionalmente sustituidos con un resto oxo(=O); restos -(CH2)t- de los grupos R1 precedentes, en los que t es un número entero de 2 a 5, que incluyen opcionalmente un doble o triple enlace carbono-carbono; y grupos R1 precedentes que, salvo H, están opcionalmente sustituidos con de 1 a 3 grupos R4; R2 es selecciona de la lista de sustituyentes proporcionada en la definición de R1, -SO2(CH2)t(arilo C6-10)m -SO2(CH2)t(heterociclo de 5-10 miembros) y -OR5, siendo t un número entero que varía de 0 a 5, restos -(CH2)t- de los grupos R2 precedentes,en los que t es un número entero de 2 a 5, que incluyen opcionalmente un doble o triple enlace carbono-carbono, y grupos R2 precedentes que están opcionalmente sustituidos con de 1 a grupos R4; o R1 y R2 pueden ser tomados junto con el nitrógeno al que está unidos cada uno para formar un anillo monocíclico o policíclico saturado de 4-10 miembros o un anillo heteroarilo de 5-10 miembros, anillos saturado y heteroarílico que incluyen opcionalmente 1 ó 2 heteroátomos seleccionados entre O, S y -N(R6)- además del nitrógeno al que están unidos R1 y R2, siendo dicho -N(R6)- opcionalmente =N- o -N= cuando R1 y R2 son tomados conjuntamente como dicho grupo heteroarílico, anillo saturado que opcionalmente puede estar parcialmente insaturado al incluir 1 ó 2 dobles enlaces carbono-carbono, y anillos saturado y heteroarílico que, incluyendo el grupo R6 de dicho -N(R6)-, están opcionalmente sustituidos con de 1 a 3 grupos R4; R3 es H, alquilo C1-10, alquenilo C2-10, alquinilo C2-10, -(CH2)t(arilo C6-10) o -(CH2)t(heterociclo de 5-10 miembros, siendo t un número entero de 0 a 5; grupo alquilo que incluye opcionalmente 1 ó 2 heterorrestos seleccionados entre O, S y -N(R6)- con la condición de que dos átomos de O, dos átomos de S o un átomo de O y un átomo de S no estén directamente unidos entre sí; grupos R3 arílico heterocíclico que están opcionalmente fusionados con un grupo arilo C610, un grupo cíclico saturado C5-8 o un grupo heterocíclico de 5-10 miembros; estando 1 ó 2 átomos de carbono de los restos heterocíclicos precedentes opcionalmente sustituidos con un resto oxo(=O); restos -(CH2)t- de los grupos R3 precedentes, en los que t es un número entero de 2 a 5, que incluyen opcionalmente un doble o triple enlace carbono-carbono; y grupos R3 precedentes que están opcionalmente sustituidos con de 1 a 5 grupos R4; cada R4 es independientemente seleccionado entre alquilo C1-10, alquenilo C2-10, alquinilo C2-10, halógeno, ciano, nitro, trifluorometilo, trifluorometoxilo, azido, -OR5, -C(O)R5, -C(O)OR5, NR6C(O)OR5, -OC8(O)R5, -NR6SO2R5, -SO2NR5R6, -NR6-C(O)R5, C(O)NR5R6, -NR5R6, -S(O)JR7 en que j es un número entero que varía de 0 a 2, -SO3H, -NR5(CR6R7)tOR6, -(CH2)t(arilo C6-10), -SO2(CH2)t(arilo C6-10), -S(CH2)t(arilo C6-10), -O-(CH2)t(arilo C6-10), -(CH2)t(heterociclo de 5-10 miembros) y -(CR6-R7)mOR6, en los que m es un número entero de 1 a 5 y t es un número de 0 a 5; grupo alquilo que contiene opcionalmente 1 ó 2 heterorrestos seleccionados entre O, S y -N(R6)- con la condición de que dos átomos O, dos átomos de S o un átomo de O y un átomo de S no estén directamente unidos entre sí; grupos R4 arílico y heterocíclico que están opcionalmente fusionados con un grupo arilo C6-19, un grupo cíclico saturado C5-8 o un grupo heterocíclico de 5-10 miembros; estando 1 ó 2 átomos de carbono de los restos heterocíclicos precedentes opcionalmente sustituidos con un resto oxo(=O); y restos alquilo, arilo y heterociclo de los grupos R4 precedentes que están opcionalmente sustituidos con de 1 a 3 sustituyentes independientemente seleccionados entre halógeno, ciano, nitro, trifluorometilo, trifluorometoxilo, azido, -NR6-SO2R5, -SO2NR5R6, -C(O)R5, -C(O)OR5, -OC(O)R5, -NR6C(O)R5, .-C(O)NR5R6, NR5R6, -(CR6R7)mOR6 en que m es un número entero de 1 a 5, -OR5 y los sustituyentes enumerados en la definición de R5; cada R5 es independientemente seleccionado entre H, alquilo C1-10, -(CH2)t-(arilo C6-10) y -(CH2)t(heterociclo de 5-10 miembros), en los que t es un número entero de 0 a 5; grupo alquilo que incluye opcionalmente 1 ó 2 heterorrestos seleccionados entre O, S y -N(R6)- con la condición de que dos átomos de O, dos átomos de S o un átomo de O y un átomo de S no estén directamente unidos entre sí; grupos R5 arílico y heterocíclico que están opcionalmente fusionados con un grupo arilo C6-10, un grupo cíclico saturado C58 o un grupo heterocíclico de 5-10 miembros; y estando los sustituyentes R5 precedentes, salvo H, opcionalmente sustituidos con de 1 a 3 sustituyentes independientemente seleccionados entre halógenos, ciano, nitro, trifluorometilo, trifluorometoxilo, azido, -C(O)R6, -C(O)OR6, -CO(O)R6, -NR6C(O)R7, -C(O)NR6R7, -NR6R7, hidroxilo, alquilo C1-6 y alcoxilo C1-6; y cada uno de R6 y R7 es independientemente H o alquilo C1-6.
ARP030102971A 2002-08-19 2003-08-15 Terapia de combinacion para enfermedades hiperproliferativas AR040995A1 (es)

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EP (1) EP1545519B1 (es)
JP (1) JP3835763B2 (es)
KR (1) KR100668539B1 (es)
CN (1) CN1681495B (es)
AP (1) AP2005003232A0 (es)
AR (1) AR040995A1 (es)
AT (1) ATE502635T1 (es)
AU (1) AU2003250483A1 (es)
BR (1) BR0313593A (es)
CA (1) CA2495962A1 (es)
CR (1) CR7693A (es)
DE (1) DE60336485D1 (es)
EA (1) EA200500234A1 (es)
EC (1) ECSP055618A (es)
ES (1) ES2362998T3 (es)
GE (1) GEP20074134B (es)
GT (1) GT200300177A (es)
HK (1) HK1079106A1 (es)
HR (1) HRP20050163A2 (es)
IL (1) IL166545A0 (es)
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MA (1) MA27385A1 (es)
MX (1) MXPA05001958A (es)
NO (1) NO20050621L (es)
OA (1) OA12905A (es)
PA (1) PA8580201A1 (es)
PE (1) PE20040993A1 (es)
PL (1) PL375713A1 (es)
RS (1) RS20050106A (es)
TN (1) TNSN05051A1 (es)
TW (1) TW200403057A (es)
WO (1) WO2004017964A1 (es)

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