AR054624A1 - DERIVADOS DE PIRROL[2, 3 - B]PIRIDINA, UN INTERMEDIARIO PARA SU PREPARACIoN, UNA COMPOSICIoN FARMACÉUTICA Y UN KIT QUE LOS COMPRENDE Y SU USO EN LA PREPARACIoN DE UN MEDICAMENTO PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR LA MODULACIoN DE LA ACTIVIDAD DE LAS PROTEíNAS KINASAS., - Google Patents

DERIVADOS DE PIRROL[2, 3 - B]PIRIDINA, UN INTERMEDIARIO PARA SU PREPARACIoN, UNA COMPOSICIoN FARMACÉUTICA Y UN KIT QUE LOS COMPRENDE Y SU USO EN LA PREPARACIoN DE UN MEDICAMENTO PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR LA MODULACIoN DE LA ACTIVIDAD DE LAS PROTEíNAS KINASAS.,

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Publication number
AR054624A1
AR054624A1 ARP060102668A ARP060102668A AR054624A1 AR 054624 A1 AR054624 A1 AR 054624A1 AR P060102668 A ARP060102668 A AR P060102668A AR P060102668 A ARP060102668 A AR P060102668A AR 054624 A1 AR054624 A1 AR 054624A1
Authority
AR
Argentina
Prior art keywords
alk
fluorine
alkylamino
optionally substituted
cr10r11
Prior art date
Application number
ARP060102668A
Other languages
English (en)
Inventor
Prabha N Ibrahim
Dean Richard Artis
Shumeye Mamo
Marika Nespi
Chao Zhang
Jiazhong Zhang
Yong-Liang Zhu
Jianming Tsai
Klaus-Peter Hirth
Gideon Bollag
Wayne Spevak
Hanna Cho
Samuel J Gillette
Guoxian Wu
Hongyao Zhu
Shenghua Shi
Original Assignee
Plexxikon Inc
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.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37033831&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR054624(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Plexxikon Inc filed Critical Plexxikon Inc
Publication of AR054624A1 publication Critical patent/AR054624A1/es

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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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Abstract

Se describen compuestos con actividad sobre las proteínas kinasas, así como métodos para utilizar dichos compuestos en medicamentos para el tratamiento de enfermedades y condiciones asociadas a la actividad aberrante de las proteínas kinasas, incluyendo las kinasas B-Raf, c-Raf-1, Fms, Jnk1, Jnk2, Jnk3, y kit, y cualquier mutacion de las mismas. Reivindicacion 1: Un compuesto de formula (1) , donde todas las sales, prodrogas, tautomeros, y isomeros de los mismos, en donde: Q tiene una estructura seleccionada del grupo de formulas (2), en el cual la ligadura atravesada por la línea ondulada indica el punto de union a A de la formula (1); Z2 es N o CR12, Z4 es N o CR14; Z5 es N o CR15; Z6 es N o CR16; L2 es seleccionado del grupo que comprende, -(CR10R11)p-NR25-(CR10R11)q-, -(CR10R11)p-O-(CR10R11)q-, -(CR10R11)p-S-(CR10R11)q-, -(CR10R11)p-C(O) -(CR10R11)q-, -(CR10R11)p-C(S)-(CR10R11)q-, -(CR10R11)p-S(O)-(CR10R11)q-, -(CR10R11)p-S(O)2-(CR10R11)q-, -(CR10R11)p-C(O)NR25- (CR10R11)q-, -(CR10R11)p-C(S)NR25-(CR10R11)q-, -(CR10R11)p-S(O)2NR25-(CR10R11)q-, -(CR10R11)p-NR25C(O)-(CR10R11)q-, -(CR10R11)p-NR25C(S)-(CR10R11)q-, -(CR10R11)p-NR25S(O)2-(CR10R11)q-; p y q son independientemente 0, 1 o 2 con la condicion, empero, de que al menos uno de entre p y q sea 0; r es 0, 1 o 2; s es 1 o 2; X es O o S; A es seleccionado del grupo que comprende -O-, -S-, -CRaRb-, -NR1-, -C(O)-, -C(S)-, -S(O)-, y -S(O)2-; Ra y Rb en cada ocasion son independientemente seleccionadas del grupo que comprende hidrogeno; fluor, -OH, -NH2, alquilo inferior, alcoxi inferior, tioalquilo inferior, mono-alquilamino, di-alquilamino, y -NR8R9, en donde la(s) cadena(s) alquilo del alquilo inferior, alcoxi inferior, tioalquilo inferior, mono- alquilamino, o di-alquilamino están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino, con la condicion, empero, que cualquier sustitucion del carbono de la cadena alquilo enlazado al O de alcoxi, S de tioalquilo o N de mono- o di-alquilamino sea fluor; o Ra y Rb se combinan para formar un cicloalquilo monociclo de 3-7 miembros o heterocicloalquilo monociclo de 5-7 miembros, en donde el cicloalquilo monociclo o heterocicloalquilo monociclo están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende halogeno, -OH, -NH2, alquilo inferior, alquilo inferior sustituido con fluor, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono- alquilamino, di-alquilamino, y cicloalquilamino; R1 es seleccionado del grupo que comprende hidrogeno, alquilo inferior, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, -C(O)R7, -C(S)R7, -C(O)NHR7, -C(S)NHR7, y -S(O)2NHR7, en donde alquilo inferior está opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, tioalquilo inferior, mono-alquilamino, di-alquilamino, y -NR8R9, en donde la(s) cadena(s) alquilo del alcoxi inferior, tioalquilo inferior, mono-alquilamino, o di-alquilamino están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino, con la condicion, empero, que cualquier sustitucion del carbono de la cadena alquilo enlazado al O de alcoxi, S de tioalquilo o N de mono- o di- alquilamino sea fluor, siempre y cuando además que cuando R1 es alquilo inferior, cualquier sustitucion del carbono del alquilo inferior enlazado al N de -NR1- sea fluor, y en donde cicloalquilo, heterocicloalquilo, arilo o heteroarilo están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende halogeno, -OH, -NH2, alquilo inferior, alquilo inferior sustituido con fluor, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino; R7 es seleccionado del grupo que comprende alquilo inferior, cicloalquilo, heterocicloalquilo, arilo, y heteroarilo, en donde alquilo inferior está opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, tioalquilo inferior, mono-alquilamino, di-alquilamino, y -NR8R9, con la condicion, empero, que cualquier sustitucion del carbono del alquilo enlazado al N de -C(O)NHR7, -C(S)NHR7 o -S(O)2NHR7 sea fluor, en donde la(s) cadena(s) alquilo del alcoxi inferior, tioalquilo interior, mono-alquilamino, o di-alquilamino están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino, con la condicion, empero, que cualquier sustitucion del carbono de la cadena alquilo enlazado al O de alcoxi, S de tioalquilo o N de mono- o di-alquilamino sea fluor, y en donde cicloalquilo, heterocicloalquilo, arilo y heteroarilo están opcionalmente sustituidos con uno o más sustituyentes seleccionados del. grupo que comprende halogeno, -OH, -NH2, alquilo inferior, alquilo inferior sustituido con fluor, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino; R4, R5, R6, R12, R14, R15, R16, R42, R43, R45, R46 y R47 son independientemente seleccionados del grupo que comprende hidrogeno, halogeno, alquilo inferior opcionalmente sustituido, alquenilo inferior opcionalmente sustituido, alquinilo inferior opcionalmente sustituido, cicloalquilo opcionalmente sustituido, heterocicloalquilo opcionalmente sustituido, arilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, -CN, -NO2, y LR26; L en cada ocasion es independientemente seleccionado del grupo que comprende -(alk)a-S-(alk)b-, -(alk)a-O-(alk)b-, -(alk)a-NR25-(alk)b-, -(alk)a-C(O)-(alk)b-, -(alk)a-C(S) -(alk)b-, -(alk)a-S(O)-(alk)b-, - (alk)a-S(O)2-(alk)b-, -(alk)a-OC(O)-(alk)b-, -(alk)a-C(O)O-(alk)b-, -(alk)a-OC(S)-(alk)b-, -(alk)a-C(S)O-(alk)b-, -(alk)a-C(O)NR25-(alk)b-, -(alk)a-C(S)NR25-(alk)b-, -(alk)a-S(O)2NR25-(alk)b-, -(alk)a-NR25C(O)-(alk)b-, -(alk)a-NR25C(S)-(alk)b-, - (alk)a-NR25S(O)2-(alk)b-, -(alk)a-NR25C(O)O-(alk)b-, -(alk)a-NR25C(S)O-(alk)b-, -(alk)a-OC(O)NR25-(alk)b-, -(alk)a-OC(S)NR25-(alk)b-, -(alk)a-NR25C(O)NR25-(alk)b-, -(alk)a-NR25C(S)NR25-(alk)b-, y -(alk)a-NR25S(O)2NR25-(alk)b-; a y b son independientemente 0 o 1; alk es alquileno C1-3 o alquileno C1-3 sustituido con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alquilo inferior, alcoxi inferior, tioalquilo inferior, mono-alquilamino, di-alquilamino, y -NR8R9, en donde alquilo inferior o la(s) cadena(s) alquilo del alcoxi inferior, tioalquilo inferior, mono-alquilamino o di-alquilamino están opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, - NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino y cicloalquilamino, con la condicion, empero, que cualquier sustitucion del carbono de la cadena alquilo enlazado al O de alcoxi, S de tioalquilo o N de mono- o di-alquilamino sea fluor; R25 en cada ocasion es independientemente seleccionado del grupo que comprende hidrogeno, alquilo inferior opcionalmente sustituido, cicloalquilo opcionalmente sustituido, heterocicloalquilo opcionalmente sustituido, arilo opcionalmente sustituido, y heteroarilo opcionalmente sustituido; R26 en cada ocasion es independientemente seleccionado del grupo que comprende hidrogeno, con la condicion, empero, que el hidrogeno no esté enlazado a ninguno de S(O), S(O)2, C(O) o C(S) de L, alquilo inferior opcionalmente sustituido, alquenilo inferior opcionalmente sustituido, con la condicion, empero, que cuando R26 sea alquenilo inferior opcionalmente sustituido, ningun carbono de alqueno de los mismos esté enlazado al N, S, O, S(O), S(O)2, C(O) o C(S) de L, alquinilo inferior opcionalmente sustituido, con la condicion, empero, que cuando R26 sea alquinilo inferior opcionalmente sustituido, ningun carbono de alquino de los mismos esté enlazado al N, S, O, S(O), S(O)2, C(O) o C(S) de L, cicloalquilo opcionalmente sustituido, heterocicloalquilo opcionalmente sustituido, arilo opcionalmente sustituido, y heteroarilo opcionalmente sustituido; R10 y R11 en cada ocasion son independientemente seleccionados del grupo que comprende hidrogeno, fluor, alquilo inferior, y alquilo inferior opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino; o dos cualquiera de R10 y R11 sobre el mismo átomo de carbono o sobre átomos de carbono adyacentes se combinan para formar un cicloalquilo monociclo de 3-7 miembros o heterocicloalquilo monociclo de 5-7 miembros, y cualquier otro R10 y R11 son independientemente seleccionados del grupo que comprende hidrogeno,: fluor, alquilo inferior, y alquilo inferior opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo que comprende fluor, -OH, -NH2, alcoxi inferior, alcoxi inferior sustituido con fluor, tioalquilo inferior, tioalquilo inferior sustituido con fluor, mono-alquilamino, di-alquilamino, y cicloalquilamino, y en donde el cicloalquilo monociclo o heterocicloalquilo monociclo están opcio
ARP060102668A 2005-06-22 2006-06-22 DERIVADOS DE PIRROL[2, 3 - B]PIRIDINA, UN INTERMEDIARIO PARA SU PREPARACIoN, UNA COMPOSICIoN FARMACÉUTICA Y UN KIT QUE LOS COMPRENDE Y SU USO EN LA PREPARACIoN DE UN MEDICAMENTO PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR LA MODULACIoN DE LA ACTIVIDAD DE LAS PROTEíNAS KINASAS., AR054624A1 (es)

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