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AR038202A1 - Compuestos de indazol utiles como inhibidores de la proteina quinasa - Google Patents

Compuestos de indazol utiles como inhibidores de la proteina quinasa

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Publication number
AR038202A1
AR038202A1 ARP030100171A ARP030100171A AR038202A1 AR 038202 A1 AR038202 A1 AR 038202A1 AR P030100171 A ARP030100171 A AR P030100171A AR P030100171 A ARP030100171 A AR P030100171A AR 038202 A1 AR038202 A1 AR 038202A1
Authority
AR
Argentina
Prior art keywords
independently selected
saturated
ring
independently
partially unsaturated
Prior art date
Application number
ARP030100171A
Other languages
English (en)
Inventor
Hayley Binch
Guy Brenchley
Julian M C Golec
Ronald Knegtel
Michael Mortimore
Sanjay Patel
Alistair Rutherford
Original Assignee
Vertex Pharma
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 Vertex Pharma filed Critical Vertex Pharma
Publication of AR038202A1 publication Critical patent/AR038202A1/es

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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
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    • C—CHEMISTRY; METALLURGY
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    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

Los compuestos son inhibidores de la proteína quinasa, en particular, son inhibidores de quinasa AKT, PKA, PDK1, p70S6K o ROCK, proteínas quinasas de mamífero involucradas en trastornos proliferativos y neurodegenerativos. Además se proporciona composiciones farmacéuticas que comprenden a los compuestos de la presente y a los métodos para utilizar dichas composiciones en el tratamiento de varios trastornos. Reivindicación 1: Un método para inhibir la quinasa AKT, PKA, PDK1, p70S6K o ROCK en: (a) un paciente; o (b) una muestra biológica; estando dicho método caracterizado porque comprende administrar a dicho paciente, o poner en contacto dicha muestra biológica con un compuesto de la fórmula (1) o una sal del mismo aceptable para uso farmacéutico, donde R1 se selecciona de halógeno, CN, N(R4)2, T-R, o T-Ar; cada T se selecciona, de manera independiente, de un enlace de valencia o una cadena de alquilideno C1-6, donde hasta dos unidades de metileno de T están, de manera opcional e independiente, reemplazadas por -O-, -N(R)-, -S-, -N(R)C(O), -C(O)N(R)-, -C(O)-, o -SO2-, T' es una cadena de alquilideno C1-6 donde hasta dos unidades de metileno de T' son reemplazadas, de manera opcional e independiente, por -O-, -N(R)-, -S-, -N(R)C(O)-, -C(O)N(R)-, -C(O)-, o -SO2; cada R se selecciona, de manera independiente, de H o un grupo alifático C1-6 opcionalmente sustituido, o: dos grupos R en el mismo N, tomados junto con el átomo de N unido allí, forman un anillo saturado, parcialmente insaturado o aromático de 5-7 miembros que tiene 1-3 heteroátomos seleccionados, de manera independiente, de N, O ó S; R2 se selecciona de Q-Ar, Q-N(R5)2, o Q-C(R)(Q-Ar)R3, donde: R y R3 forman de manera opcional, un anillo saturado o parcialmente insaturado de 5-7 miembros que tiene 0-4 heteroátomos seleccionados, de manera independiente, de N, O, o S; cada Q se selecciona, de manera independiente, de un enlace de valencia o una cadena de alquilideno C1-4; cada Ar es, independientemente, un anillo opcionalmente sustituido, seleccionado entre un anillo monocíclico, saturado, parcialmente insaturado o completamente insaturado de 5-7 miembros que tiene de 0-4 heteroátomos seleccionados, de manera independiente, de N, O, o S, o un anillo bicíclico saturado, parcialmente insaturado o completamente insaturado de 8-10 miembros que tiene de 0-4 heteroátomos seleccionados, de manera independiente, de N, O, o S; R3 se selecciona de R', Ar1, Q-OR5, Q-OC(O)R5, Q-CONHR5, Q-OC(O)NHR5, Q-SR5, Q-N(R4)2, N(R)(Q-Ar), N(R)C(O)Q-N(R4)2, o N(R)Q-N(R4)2; R' es un grupo alifático C1-6 opcionalmente sustituido; cada R4 se selecciona de manera independiente de R, COR5, CO2R5, CON(R5)2, SO2R5, SO2N(R5)2, o Ar1; cada R5 se selecciona, de manera independiente, de R o Ar; V1, V2, y V3 se seleccionan, de manera independiente, de N o C(R6); cada R6 se selecciona, de manera independiente de R, Ar1, halógeno, CN, NO2, OR, SR, N(R4)2, N(R)COR, N(R)CON(R4)2, N(R)C(O)OR, CON(R4)2, OC(O)N(R4)2, CO2R, OC(O)R, N(R)SO2R, N(R)SO2N(R4)2, SO2R, o SO2N(R4)2; y cada Ar1 se selecciona, de manera independiente, de un anillo monocíclico, opcionalmente sustituido, saturado, parcialmente insaturado o completamente insaturado de 5-7 miembros que tiene 0-4 heteroátomos seleccionados, de manera independiente, de N, O, o S; con la condición de que; cuando V1, V2 y V3 son, cada uno, CH y R1 es H, entonces R2 es Q-C(R)(Q-Ar)R3, donde R3 es diferente de R', Q-OC(O)R5 o OCH2fenilo.
ARP030100171A 2002-01-25 2003-01-21 Compuestos de indazol utiles como inhibidores de la proteina quinasa AR038202A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US35159702P 2002-01-25 2002-01-25

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AR038202A1 true AR038202A1 (es) 2005-01-05

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ARP030100171A AR038202A1 (es) 2002-01-25 2003-01-21 Compuestos de indazol utiles como inhibidores de la proteina quinasa

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US (1) US7041687B2 (es)
EP (3) EP2295413A1 (es)
JP (2) JP4718118B2 (es)
KR (2) KR20040078676A (es)
CN (1) CN1812973B (es)
AR (1) AR038202A1 (es)
AU (1) AU2003212833C1 (es)
CA (1) CA2473986C (es)
IL (1) IL163117A (es)
MX (1) MXPA04007126A (es)
NO (1) NO328041B1 (es)
PL (1) PL371512A1 (es)
RU (1) RU2004125852A (es)
TW (1) TW200306819A (es)
WO (1) WO2003064397A1 (es)

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