AR050343A1 - Derivados de pirimidin-urea - Google Patents

Derivados de pirimidin-urea

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Publication number
AR050343A1
AR050343A1 ARP050102624A ARP050102624A AR050343A1 AR 050343 A1 AR050343 A1 AR 050343A1 AR P050102624 A ARP050102624 A AR P050102624A AR P050102624 A ARP050102624 A AR P050102624A AR 050343 A1 AR050343 A1 AR 050343A1
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Argentina
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alkyl
substituted
hydroxyl
atoms
halogen
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ARP050102624A
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Novartis Ag
Irm Llc
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34855683&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR050343(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag, Irm Llc filed Critical Novartis Ag
Publication of AR050343A1 publication Critical patent/AR050343A1/es

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    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
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    • 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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    • 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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    • C07D409/12—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

Abstract

La presente se refiere a derivados de pirimidin-urea, procesos para la preparacion de estos compuestos, a composiciones farmacéuticas que los contienen, al uso de los mismos opcionalmente en combinacion con uno o más compuestos farmacéuticamente activos diferentes, para la terapia de una enfermedad que responda a la inhibicion de la actividad de quinasa de proteína, y a un método para el tratamiento de dicha enfermedad. Reivindicacion 1: Un compuesto de la formula (1) en donde: n es 0, 1, 2, 3, 4 o 5; X, Y, y Z se seleccionan cada uno independientemente a partir de N o C-R5, en donde cuando menos dos de X, Y, y Z son N; y X1 es O; R1, R2, R3, y R4, si están presentes, se seleccionan cada uno independientemente a partir de una fraccion orgánica o inorgánica, en donde la fraccion inorgánica se selecciona especialmente a partir de halogeno, en especial Cl, hidroxilo, ciano, azo (N=N=N), nitro; y en donde la fraccion orgánica está sustituida o insustituida, y puede unirse por medio de un enlazador, -L1-, seleccionándose en especial la fraccion orgánica a partir de H, alifático inferior (en especial alifático de 1, 2, 3, o 4 átomos de C), por ejemplo alquilo inferior, alquenilo inferior, alquinilo inferior; amino; guanidino; hidroxi-guanidino; formamidino; isotioureido; ureido; mercapto; carboxilo; sulfo; sulfamoilo; carbamoílo; C(O)H, u otro acilo; aciloxilo; hidroxilo sustituido; un grupo cíclico sustituido o insustituido, por ejemplo el grupo cíclico (ya sea sustituido o insustituido) puede ser cicloalquilo, por ejemplo ciclohexilo, fenilo, pirrol, imidazol, pirazol, isoxazol, oxazol, tiazol, piridazina, pirimidina, pirazina, piridilo, indol, isoindol, indazol, purina, indolizidina, quinolina, isoquinolina, quinazolina, pteridina, quinolizidina, piperidilo, piperazinilo, pirrolidina, morfolinilo, o tiomorfolinilo, y, por ejemplo, hidroxilo sustituido o alifático inferior sustituido puede estar sustituido por estos grupos cíclicos sustituidos o insustituidos; y -L1- tiene 1, 2, 3, 4 o 5 átomos en la cadena (por ejemplo, seleccionados a partir de C, N, O, y S), y seleccionándose opcionalmente a partir de (i) alquilo de 1, 2, 3, o 4 átomos de C, tal como un grupo alquilo opcionalmente interrumpido y/o terminado por. Un enlace -O-, -C(O)-, o -NRa-; -O-; -S-; -C(O)-; ciclopropilo (considerado por tener dos átomos en la cadena), y combinaciones químicamente apropiadas de los mismos; y -NRa-, en donde Ra es H, hidroxilo, hidrocarbiloxilo, o hidrocarbilo, en donde hidrocarbilo está opcionalmente interrumpido por un enlace -O- o -NH-, y por ejemplo, se puede seleccionar a partir de un grupo alifático (por ejemplo, que tenga de 1 a 7 átomos de C, por ejemplo 1, 2, 3, o 4), cicloalquilo, en especial ciclohexilo, cicloalquenilo, en especial ciclohexenilo, u otro grupo carbocíclico, por ejemplo fenilo; en donde la fraccion de hidrocarbilo está sustituida o insustituida; en donde R1 también puede representar -X5NR7R8, -X5NR7X5NR7R8, -X5NR7X5C(O)OR8, -X5OR7, -X5R7 y -X5S(O)0-2R7; en donde X5 es un enlace o alquileno de 1 a 4 átomos de C opcionalmente sustituido por 1 a 2 radicales de alquilo C1-6; R7 se selecciona a partir de H, alquilo C1-6, arilo C6-10-alquilo C0-4, heteroarilo C5-10-alquilo C0-4, cicloalquilo C3-10-alquilo C0-4 y heterocicloalquilo C3-10-alquilo C0-4; y R8 se selecciona a partir de H y alquilo C1-6; o R7 y R8 junto con el átomo de N con el que están unidos R7 y R8 forman heteroarilo o heterocicloalquilo; en donde cualquier arilo, heteroarilo, cicloalquilo y heterocicloalquilo de R7 o la combinacion de R7 y R8 puede ser opcionalmente sustituido con 1 a 3 radicales independientemente seleccionados a partir de halogeno, nitro, ciano, hidroxilo, alquilo C1-6, alcoxilo C1-6, alquilo sustituido por halogeno, alcoxilo sustituido por halogeno, -X5NR9R10, -X5OR9, -X5NR9S(O)2R10, -X5NR9S(O)R10, -X5NR9SR10, -X5C(O)NR9R10, -X5NR9C(O)NR9R10, -X5NR9C(O)R10, - X5NR9X5NR9R10, -X5NR9X5OR9, -X5NR9C(=NR9)NR9R10, -X5S(O)0-2R11, -X5NR9C(O)R10, X5NR9C(O)R11, -X5R11, -X5C(O)OR10, -X5S(O)2NR9R10, -X5S(O)NR9R10 y -X5SNR9R10; en donde X5 es un enlace o alquileno C1-4; R9 y R10 se seleccionan independientemente a partir de H y alquilo C1-4; y R11 es heterocicloalquilo C3-10 opcionalmente sustituido con 1 a 3 radicales seleccionados a partir de alquilo C1-4, -X5NR9X5NR9R9, X5NR9X5OR9 y -X5OR9; en donde R3 puede también representar de una manera alternativa H, alquilo C1-4, arilo C6-10-alquilo C0-4; en donde cualquier alquilo, arilo, heteroarilo, cicloalquilo, o heterocicloalquilo de R3 está opcionalmente sustituido por 1 a 3 radicales seleccionados a partir de halogeno, alquilo C1-4, -X5S(O)0-2NR9R10 y - X5OR9; en donde X5, R9 y R10 son como se describen anteriormente; cada R4 es igual o diferente, y se selecciona a partir de una fraccion orgánica o inorgánica, por ejemplo, cada R4 es igual o diferente, y se selecciona a partir de halogeno; hidroxilo, hidroxilo protegido, por ejemplo trialquil-silil-hiroxilo; amino; amidino; guanidino; hidroxi-guanidino; formamidino; isotioureido; ureido; mercapto; C(O)H u otro acilo; aciloxilo; carboxilo; sulfo; sulfamoilo; carbamoílo; ciano; azo; nitro; alifático de 1 a 7 átomos de C opcionalmente sustituido por uno o más halogenos y/o uno o dos grupos funcionales seleccionados partir de hidroxilo; hidroxilo protegido, por ejemplo trialquil-silil-hidroxilo; amino; amidino; guanidino; hidroxi-guanidino; formamidino; isotioureido; ureido,; mercapto; C(O)H u otro acilo; aciloxilo; carboxilo; sulfo; sulfamoilo; carbamoílo; ciano; aza; o nitro; estando a su vez todos los grupos hidroxilo, amino, amidino, guanidino, hidroxi-guanidino, formamidino, isotioureido, ureido, mercapto, carboxilo, sulfo, sulfamoilo, y carbamoílo anteriormente mencionados, opcionalmente sustituidos sobre cuando menos un heteroátomo por uno, o donde sea posible más grupos alifáticos de 1 a 7 átomos de C, en donde uno de los radicales R4 también puede representar un resto de formula (2) en donde L1 es un enlazador; m es 0, 1, 2, 3, 4 o 5; L1 es un enlazador; y R16, si está presente, se selecciona cada uno independientemente a partir de una fraccion orgánica o inorgánica, en donde la fraccion inorgánica se selecciona en especial a partir de halogeno, especialmente Cl, hidroxilo, ciano, aza (N=N=N), nitro; y en donde la fraccion orgánica está sustituida o insustituida, y se puede unir por medio de un enlazador, -L2-, seleccionándose en especial la fraccion orgánica a partir de H, alifático inferior (en especial alifático de 1, 2, 3, o 4 átomos de C), por ejemplo alquilo inferior, alquenilo inferior, alquinilo inferior; amino; guanidino; hidroxi-guanidino; formamidino; isotioureido; ureido; mercapto; C(O)H u otro acilo; aciloxilo; hidroxilo sustituido, carboxilo; sulfo; sulfamoilo; carbamoílo; un grupo cíclico sustituido o insustituido, por ejemplo el grupo cíclico (ya sea sustituido o insustituido) puede ser cicloalquilo, por ejemplo ciclohexilo, fenilo, pirrol, imidazol, pirazol, isoxazol, oxazol, tiazol, piridazina, pirimidina, pirazina, piridilo, indol, isoindol, indazol, purina, indolizidina, quinolina, isoquinolina, quinazolina, pteridina, quinolizidina, piperidilo, piperazinilo, pirrolidina, morfolinilo, o tiomorfolinilo, y, por ejemplo, alifático inferior sustituido o hidroxilo sustituido puede estar sustituido por estos grupos cíclicos sustituidos o insustituidos, L1 y L2 se seleccionan cada uno independientemente a partir de las fracciones que tienen 1, 2, 3, 4 o 5 átomos en la cadena (por ejemplo, se seleccionan a partir de C, N, O y S), y opcionalmente se seleccionan a partir de (i) alquilo de 1, 2, 3, o 4 átomos de c, estando este grupo alquilo opcionalmente interrumpido y/o terminado por un enlace -O-, -C(O)-, o -NRa-; -O-; -S-; -C(O)-; ciclopropilo (considerado por tener dos átomos en la cadena), y combinaciones químicamente apropiadas de los mismos; y -NRa-, en donde Ra es H, hidroxilo, hidroxicarbiloxilo, o hidrocarbilo, en donde hidrocarbilo está opcionalmente interrumpido por un enlace -O- o -NH-, y , por ejemplo, se puede seleccionar a partir de un grupo alifático (por ejemplo, que tenga de 1 a 7 átomos de C, por ejemplo 1, 2, 3, o 4), cicloalquilo, en especial ciclohexilo, cicloalquenilo, en especial ciclohexenilo, u otro grupo carbocíclico, por ejemplo fenilo; en donde la fraccion de hidrocarbilo está sustituida o insustituida; o R4 es un radical -NHC(O)R45 en donde R45 se selecciona a partir de arilo C6-10-alquilo C0-4, heteroarilo C5-10-alquilo C0-4, cicloalquilo C3-10-alquilo C0-4 y heterocicloalquilo C3-10-alquilo C0-4; en donde cualquier arilo, heteroarilo, cicloalquilo, o heterocicloalquilo de R45 está opcionalmente sustituido con 1 a 3 radicales seleccionados a partir de halogeno, hidroxilo, alquilo C1-4, alcoxilo C1-4, alquilo C1-4 sustituido por halogeno, alcoxilo C1-4 sustituido por halogeno, y heterociclo C3-8-alquilo C0-4; en donde cualquier sustituyente de heterocicloalquilo de R4 está opcionalmente sustituido por 1 a 3 radicales de alquilo C1-4; o sales farmacéuticamente aceptables, hidratos, solvatos, éteres, N-oxidos, derivados protegidos, isomeros individuales y mezclas de isomeros de los mismos, o profármacos de los mismos, excluyendo los compuestos que sean un compuesto de la formula (1) en donde: (A) n es 0; R3 es H; Y y Z son N; X es N, C-SO2(NH), o C-NO2 (o en una modalidad de exclusion más amplia, cualquier grupo C-R5); R2 es H, SCH2CH=CH2, o SMe; y R1 es de la formula NR'Rö, en donde R' y Rö, junto con su átomo de N adjunto, forman morfolino, o uno de R' y Rö es H y el otro es fenilo, fenilo sustituido por un solo sustituyente seleccionado a partir de Me y Cl, o es -C(O)NHPh; (B) n es 1, R4 es metoxilo; R3 es H; X es CH; Y y Z son N; R1 es NH2; y R2 es H o SMe; (C) n es 1; R4 es Cl; R3 es etilo; X, Y, y Z son N; y uno de R1 y R2 es H, mientras que el otro es Net2; o (D) n es 2; un R4 es met-Cl, y el otro es para-metilo, R3 es H; X, Y, y Z son N; y uno de R1 y R2 es H, mientras que el otro
ARP050102624A 2004-06-24 2005-06-24 Derivados de pirimidin-urea AR050343A1 (es)

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US58242504P 2004-06-24 2004-06-24
GBGB0512324.5A GB0512324D0 (en) 2005-06-16 2005-06-16 Organic compounds

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AR050343A1 true AR050343A1 (es) 2006-10-18

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