AR103064A1 - Compuestos moduladores de fxr (nr1h4) - Google Patents

Compuestos moduladores de fxr (nr1h4)

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Publication number
AR103064A1
AR103064A1 ARP150104131A ARP150104131A AR103064A1 AR 103064 A1 AR103064 A1 AR 103064A1 AR P150104131 A ARP150104131 A AR P150104131A AR P150104131 A ARP150104131 A AR P150104131A AR 103064 A1 AR103064 A1 AR 103064A1
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alkyl
alkylene
group
halo
cycloalkyl
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ARP150104131A
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English (en)
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Xu Jianjun
j watkins William
C Schmitt Aaron
e kropf Jeffrey
S Currie Kevin
A Blomgren Peter
Kremoser Claus
Kinzel Olaf
Gege Christian
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Gilead Sciences Inc
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Publication of AR103064A1 publication Critical patent/AR103064A1/es

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    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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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
    • C07D471/08—Bridged systems

Abstract

Compuestos que se unen al NR1H4 (FXR) y actúan como agonistas de FXR. Además, el uso de los compuestos para la preparación de un medicamento para el tratamiento de enfermedades y/o condiciones por unión de dichos compuestos a dicho receptor nuclear y un proceso para la síntesis de dichos compuestos. Reivindicación 1: Un compuesto caracterizado porque es de acuerdo con la fórmula (1), un enantiómero, diasterómero, tautómero, solvato, profármaco o sal farmacéuticamente aceptable del mismo, donde R se selecciona entre el grupo que consiste en hidrógeno, halógeno, C₁₋₆-alquilo, C₂₋₆-alquenilo, C₂₋₆-alquinilo, halo-C₁₋₆-alquilo, C₀₋₆-alquilen-R⁷, C₀₋₆-alquilen-O-R⁷, C₀₋₆-alquilen-CN, C₀₋₆-alquilen-NR⁷R⁸, O-C₃₋₁₀-cicloalquilo, O-C₁₋₆-alquilen-O-R⁷, O-C₃₋₁₀-heterocicloalquilo, C₀₋₆-alquilen-CO₂R⁷, C₀₋₆-alquilen-C(O)R⁷, C₀₋₆-alquilen-C(O)NR⁷R⁸, C₀₋₆-alquilen-C(O)NR⁷SO₂R⁷, C₀₋₆-alquilen-N(R⁷)C(O)R⁷, C₀₋₆-alquilen-SOˣ-R⁷, C₀₋₆-alquilen-SO₃H, C₀₋₆-alquilen-SO₂-NR⁷R⁸, C₀₋₆-alquilen-SO₂-NR⁸COR⁷, C₀₋₆-alquilen-N(R⁷)SO₂-R⁸, y C₀₋₆-alquilen-SO₂-C₃₋₁₀-heterocicloalquilo, donde alquileno, cicloalquilo, heterocicloalquilo y heteroarilo de 5 ó 6 miembros no están sustituidos o están sustituidos con 1 a 4 sustituyentes seleccionados en forma independiente entre el grupo que consiste en halógeno, CN, C₁₋₃-alquilo, halo-C₁₋₃-alquilo, OH, oxo, CO₂H, SO₃H, O-C₁₋₃-alquilo y O-halo-C₁₋₃-alquilo; R⁷ se selecciona en forma independiente entre el grupo que consiste en hidrógeno, C₁₋₆-alquilo, halo-C₁₋₆-alquilo, C₀₋₆-alquilen-C₃₋₈-cicloalquilo, C₀₋₆-alquilen-C₃₋₈-heterocicloalquilo, heteroarilo de 5 ó 6 miembros y fenilo, donde alquilo, alquileno, cicloalquilo, heterocicloalquilo, fenilo y heteroarilo no están sustituidos o están sustituidos con 1 a 6 sustituyentes seleccionados en forma independiente entre el grupo que consiste en halógeno, CN, OH, oxo, CO₂H, C₁₋₃-alquilo, halo-C₁₋₃-alquilo, O-C₁₋₃-alquilo, O-halo-C₁₋₃-alquilo, SO₃H y SO₂-C₁₋₃-alquilo; R⁸ se selecciona en forma independiente entre el grupo que consiste en hidrógeno, C₁₋₆-alquilo, halo-C₁₋₆-alquilo y C₃₋₆-cicloalquilo; o R⁷ y R⁸ cuando se toman junto con el nitrógeno al cual están unidos pueden formar un anillo de 3 a 8 miembros que contiene átomos de carbono y que contiene opcionalmente 1 ó 2 heteroátomos seleccionados entre O, S o N, donde el anillo no está sustituido o está sustituido con 1 a 4 sustituyentes seleccionados en forma independiente entre el grupo que consiste en fluoro, OH, oxo, C₁₋₄-alquilo y halo-C₁₋₄-alquilo; A es un arilo monocíclico o bicíclico de 6 - 10 miembros o un heteroarilo monocíclico o bicíclico de 5 - 10 miembros que contiene 1 a 5 heteroátomos seleccionados en forma independiente entre el grupo que consiste en N, O y S, donde arilo y heteroarilo no están sustituidos o están sustituidos con uno o dos grupos seleccionados en forma independiente entre el grupo que consiste en OH, halógeno, CN, O-C₁₋₆-alquilo, O-halo-C₁₋₆-alquilo, C₁₋₆-alquilo, halo-C₁₋₆-alquilo, C₃₋₆-cicloalquilo y halo-C₃₋₆-cicloalquilo; B es un anillo C₅₋₈-cicloalquilo o, si Y es N, entonces es B un C₄₋₈-heterocicloalquilo o C₄₋₈-heterocicloalquilo en puente que contiene un átomo de nitrógeno, y donde el sustituyente Q no es directamente adyacente al sustituyente A; Q se selecciona entre el grupo que consiste en fenilo, piridilo, tiazolilo, tiofenilo, pirimidilo, oxazolilo, pirazolilo, imidazolilo y triazolilo, cada uno no sustituido o sustituido con uno o dos grupos seleccionados en forma independiente entre el grupo que consiste en halógeno; C₁₋₄-alquilo, halo-C₁₋₄-alquilo, C₁₋₄-alcoxi o halo-C₁₋₄-alcoxi; Y se selecciona entre N, CH o CF; Z se selecciona entre el grupo de fórmulas (2), donde L se selecciona entre el grupo que consiste en una unión, C₁₋₃-alquileno y C₁₋₃-alquilen-O-; Y se selecciona entre fenilo, piridilo, N-óxido de piridilo, pirimidilo, piridinonilo, pirimidinonilo, C₄₋₈-cicloalquilo, y C₄₋₈-heterocicloalquilo, donde fenilo, piridilo, N-óxido de piridilo, pirimidilo, piridinonilo, pirimidinonilo, C₄₋₈-cicloalquilo y C₄₋₈-heterocicloalquilo están sustituidos con R² y R³ y opcionalmente sustituidos una o dos veces con un grupo seleccionado entre fluoro, cloro, CN, NH₂, NH(C₁₋₃-alquilo), N(C₁₋₃-alquil)₂, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, OH, C₁₋₃-alcoxi, fluoro-C₁₋₃-alcoxi, C₃₋₆-cicloalquilo y fluoro-C₃₋₆-cicloalquilo; R¹ se selecciona entre el grupo que consiste en C₁₋₄-alquilo y C₃₋₆-cicloalquilo, donde C₁₋₄-alquilo no está sustituido o está, sustituido con 1 a 3 sustituyentes seleccionados en forma independiente entre el grupo que consiste en fluoro, hidroxi, C₁₋₃-alcoxi y fluoro-C₁₋₃-alcoxi, y C₃₋₆-cicloalquilo no está sustituido o está sustituido con 1 a 3 sustituyentes seleccionados en forma independiente entre el grupo que consiste en fluoro, hidroxi, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, C₁₋₃-alcoxi y fluoro-C₁₋₃-alcoxi; R² y R³ se seleccionan en forma independiente entre el grupo que consiste en hidrógeno, halógeno, C₁₋₃-alquilo, halo-C₁₋₃-alquilo, C₁₋₃-alcoxi, halo-C₁₋₃-alcoxi, ciclopropilo y fluoro-ciclopropilo; R⁴ se selecciona en forma independiente entre halógeno, C₁₋₃-alquilo, halo-C₁₋₃-alquilo, C₁₋₃-alcoxi, halo-C₁₋₃-alcoxi, C₃₋₆-cicloalquilo, y fluoro-C₃₋₆-cicloalquilo; R⁵ se selecciona entre el grupo que consiste en hidrógeno, fluoro, CH₃, CHF₂ y CF₃; n se selecciona entre 0, 1, 2, 3 y 4; y x se selecciona entre 0, 1 y 2.
ARP150104131A 2014-12-17 2015-12-17 Compuestos moduladores de fxr (nr1h4) AR103064A1 (es)

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