AR087753A1 - Compuestos y composiciones como inhibidores de la quinasa c-kit - Google Patents

Compuestos y composiciones como inhibidores de la quinasa c-kit

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Publication number
AR087753A1
AR087753A1 ARP120103223A AR087753A1 AR 087753 A1 AR087753 A1 AR 087753A1 AR P120103223 A ARP120103223 A AR P120103223A AR 087753 A1 AR087753 A1 AR 087753A1
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independently selected
substituted
membered
unsubstituted
heteroatoms
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Michael James Petrassi Hank
Loren Jon
Nguyen Bao
Yeh Vince
Liu Xiaodong
Molteni Valentina
Nabakka Juliet
Li Xiaolin
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Irm Llc
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    • 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
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
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    • A—HUMAN NECESSITIES
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Abstract

Son útiles como inhibidores de la proteína quinasa, así como también métodos para utilizar estos compuestos para tratar, aliviar o prevenir un trastorno asociado con la actividad anormal o desregulada de la quinasa. En algunas realizaciones, la presente proporciona métodos para utilizar estos compuestos para tratar, aliviar o prevenir enfermedades o trastornos que implican la activación anormal de c-kit o quinasas c-kit y PDGFR (PDGFRa, PDGFRb). Reivindicación 1: Un compuesto de la fórmula (1) ó la fórmula (2), ó una sal farmacéuticamente aceptable del mismo, en donde: m es 1 y R²⁰ se selecciona a partir de H, halo, alquilo C₁₋₆, haloalquilo C₁₋₆, haloalcoxilo C₁₋₆, deuterio, alquilo C₁₋₆ deuterado, -CN, -(CR⁹₂)ₙOR⁴, -C(O)R⁴, -(CR⁹₂)ₙC(=O)OR⁴, R¹⁰, -(CR⁹₂)ₙR¹⁰, -((CR⁹₂)ₙO)ₜR⁴, -(CR⁹₂)ₙO(CR⁹₂)ₙR⁷, -(CR⁹₂)ₙC(=O)R⁴, -C(=O)N(R⁴)₂, -OR⁴, y -(CR⁹₂)ₙCN; ó m es 4 y R²⁰ es deuterio; R¹ se selecciona a partir de alquilo C₁₋₆ y halo; cada R¹¹ se selecciona independientemente a partir de H, halo y alquilo C₁₋₆; L¹ es un enlace, -NH- ó -C(O)NH-; L² es -(CR⁹₂)ₙ-, -CHR⁶-, -(CR⁹₂)ₙO-, -NH-, -(CR⁹₂)ₙC(=O)-, -C(=O)O(CR⁹₂)ₙ-, -(CR⁹₂)ₙOC(=O)NR⁴-, -(CR⁹₂)ₙNR⁴C(=O)(CR⁹₂)ₙ-, -(CR⁹₂)ₙNR⁴C(=O)-, ó -(CR⁹₂)ₙNR⁴C(=O)O; R² es R³ ó L²R³; R³ se selecciona a partir de un heterocicloalquilo no sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, una piperidinona, una oxazolidin-2-ona, pirrolidinona, una pirrolidin-2-ona y un heterocicloalquilo sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, en donde el heterocicloalquilo sustituido de 4 - 6 miembros de R³ se sustituye con 1 - 4 sustituyentes independientemente seleccionados a partir de alquil C₁₋₆, halo, -CN, haloalquilo C₁₋₆, -OR⁴, -C(=O)OR⁴, -C(=O)R⁴, -C(=O)R⁷, -C(=O)OR⁵, -(CR⁹₂)ₙOR⁴, -O(CR⁹₂)ₙOR⁴, -C(=O)O(CR⁹₂)ₙOR⁴, -N(R⁴)₂, -C(=O)NR⁴₂, -NR⁴C(=O)OR⁴, -NR⁴C(=O)(CR⁹₂)ₙOR⁴, -NR⁴(CR⁹₂)ₙOR⁴, -NR⁴S(=O)₂R⁴, -N(C(=O)OR⁴)₂, R⁸, -(CR⁹₂)ₙR⁸, alcoxilo C₁₋₆ deuterado, -S(=O)₂R⁴, -S(=O)₂R⁷, -S(=O)₂R⁸, -S(=O)₂N(R⁴)₂, -S(=O)₂NHC(=O)OR⁴, -S(=O)₂(CR⁹₂)ₙC(=O)OR⁴, S(=O)₂(CR⁹₂)ₙOR⁴, un dioxolano espiro unido, un dioxolano espiro unido el cual se sustituye con alquilo C₁₋₆, un dioxano espiro unido, un tetrahidrofuranilo espiro unido, un oxetano espiro unido, una ciclobutanona espiro unida, un ciclobutanol espiro unido, un puente de alquilo C₁, un heterocicloalquilo no sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S y un heterocicloalquilo de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S sustituido con 1 - 3 sustituyentes independientemente seleccionados a partir de alquilo C₁₋₆, halo, haloalquilo C₁₋₆, haloalcoxilo C₁₋₆, -OR⁴ y R⁸; cada R⁴ se selecciona independientemente a partir de H y alquilo C₁₋₆; R⁵ es un cicloalquilo C₃₋₈ no sustituido, un heterocicloalquilo no sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N u O ó un cicloalquilo C₃₋₈ sustituido con 1 - 3 sustituyentes independientemente seleccionados a partir de alquilo C₁₋₆; cada R⁶ se selecciona independientemente a partir de -NR⁴C(O)OR⁴, -OR⁴ y -(CR⁹₂)ₙOR⁴; cada R⁷ se selecciona independientemente a partir de haloalquilo C₁₋₆; R⁸ se selecciona a partir de un fenilo no sustituido, heteroarilo no sustituido de 5 - 6 miembros con 1 - 3 heteroátomos independientemente seleccionados a partir de N, O y S, un heteroarilo no sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, un heterocicloalquilo no sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un cicloalquilo C₃₋₈ no sustituido, un heteroarilo sustituido de 5 - 6 miembros con 1 - 3 heteroátomos independientemente seleccionados a partir de N, O y S, un fenilo sustituido, un heteroarilo sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, un heterocicloalquilo sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un cicloalquilo C₃₋₈ sustituido, un tetrahidro-1H-oxazolo[3,4-a]pirazin-3(5H)-ona, una oxazolidin-2-ona, pirrolidinona y una pirrolidin-2-ona, en donde el fenilo sustituido, el heteroarilo sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, el heteroarilo sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, sustituido cicloalquilo C₃₋₈ y heterocicloalquilo sustituido de 4 - 6 miembros de R⁸ son sustituidos con 1 - 3 sustituyentes independientemente seleccionados a partir de alquilo C₁₋₆, -(C(R⁹)₂)ₙOR⁴, -(C(R⁹)₂)ₙR⁵, -(C(R⁹)₂)ₙC(O)OR⁴, -C(O)OR⁴ y -S(O)₂R⁴; cada R⁹ se selecciona independientemente a partir de H y alquilo C₁₋₆; R¹⁰ se selecciona a partir de un fenilo no sustituido, heteroarilo no sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un heteroarilo no sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, un heterocicloalquilo no sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un cicloalquilo C₃₋₈ no sustituido, un heteroarilo sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un fenilo sustituido, un heteroarilo sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, un heterocicloalquilo sustituido de 4 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, un cicloalquilo C₃₋₈ sustituido, una oxazolidin-2-ona, pirrolidinona y una pirrolidin-2-ona, en donde el fenilo sustituido, el heteroarilo sustituido de 5 - 6 miembros con 1 - 2 heteroátomos independientemente seleccionados a partir de N, O y S, el heteroarilo sustituido de 5 miembros con 1 - 4 heteroátomos seleccionados a partir de N, cicloalquilo C₃₋₈ sustituido y heterocicloalquilo sustituido de 4 - 6 miembros de R⁸ son sustituidos con 1 - 3 sustituyentes independientemente seleccionados a partir de alquilo C₁₋₆ [Me], -(C(R⁹)₂)ₙOR⁴, -(C(R⁹)₂)ₙR⁵, -(C(R⁹)₂)ₙC(O)OR⁴ y -S(O)₂R⁴; t es 1, 2 ó 3; y cada n se selecciona independientemente a partir de 1, 2, 3 y 4.
ARP120103223 2011-09-01 2012-08-31 Compuestos y composiciones como inhibidores de la quinasa c-kit AR087753A1 (es)

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EP (1) EP2751104B1 (es)
JP (1) JP6134319B2 (es)
KR (1) KR101962495B1 (es)
CN (1) CN103797011B (es)
AP (1) AP2014007493A0 (es)
AR (1) AR087753A1 (es)
AU (1) AU2012302042B2 (es)
BR (1) BR112014004560A2 (es)
CA (1) CA2845169C (es)
CL (1) CL2014000492A1 (es)
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