ES2620668T3 - Derivados de amidas y sulfonamidas amido espirocíclicas - Google Patents

Derivados de amidas y sulfonamidas amido espirocíclicas Download PDF

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ES2620668T3
ES2620668T3 ES13755811.0T ES13755811T ES2620668T3 ES 2620668 T3 ES2620668 T3 ES 2620668T3 ES 13755811 T ES13755811 T ES 13755811T ES 2620668 T3 ES2620668 T3 ES 2620668T3
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alkyl
heteroaryl
heterocycloalkyl
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substituted
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Kenneth W. Bair
Timm R. Baumeister
Peter Dragovich
Xiongcai LIU
Snahel PATEL
Mark Zak
Guiling Zhao
Yamin ZHANG
Xiaozhang Zheng
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Genentech Inc
Forma TM LLC
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Forma TM LLC
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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Abstract

Un compuesto de Fórmula I: **Fórmula** en la que: R es (a) un heteroarilo bicíclico de 8, 9 o 10 miembros que comprende un heteroátomo seleccionado entre N, S y O, y uno, dos o tres átomos de N adicionales, en la que dicho heteroarilo bicíclico está sin sustituir o sustituido con uno o más sustituyentes seleccionados entre el grupo que consiste en deuterio, amino, alquilamino, dialquilamino, alquilo, halo, ciano, haloalquilo, hidroxi, hidroxialquilo y alcoxi, y en la que uno o más átomos de N de dicho heteroarilo bicíclico son opcionalmente un N-óxido; o (b) un anillo de heterocicloalquilo unido a nitrógeno de cinco o seis miembros condensado a un fenilo o heteroarilo monocíclico de cinco o seis miembros, en la que dicho fenilo o heteroarilo está sin sustituir o sustituido con uno o más sustituyentes seleccionados entre el grupo que consiste en deuterio, amino, alquilamino, dialquilamino, alquilo, halo, ciano, haloalquilo, hidroxi, hidroxialquilo y alcoxi; y R1 es H, -(alquileno C1-4)0-1C(O)Ra, -(alquileno C1-4)0-1CO2Ra, -(alquileno C1-4)0-1S(O)Ra, -(alquileno C1-4)0-1SO2Ra, -C(O)NH(Ra),-C(O)N(Ra)2, o -C(O)C(O)NH(Ra); en la que cada Ra es independientemente (1) alquilo, sin sustituir o sustituido con uno o más sustituyentes Rm, en la que cada Rm se selecciona independientemente entre el grupo que consiste en hidroxi, - NRbRc, alcoxi, ciano, halo, -C(O)alquilo, -CO2alquilo, -CONRbRc, -S(O)alquilo, -SO2alquilo, -SO2NRbRc, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, fenoxi y -O-alquil-OH; en la que Rb es H o alquilo; Rc es H, alquilo, alcoxialquilo, haloalquilo, -C(O)alquilo, -CO2alquilo, -SO2alquilo, -C(O)NH2, o C(O)H; y cada grupo arilo, heteroarilo, cicloalquilo y heterocicloalquilo en Rm está sin sustituir o sustituido con uno o más sustituyentes seleccionados independientemente entre el grupo que consiste en alquilo, haloalquilo, hidroxi, -NRbRc, alcoxi, haloalcoxi, ciano, halo, oxo, -C(O)alquilo, -CO2alquilo, -C(O)-heterocicloalquilo, -CONRbRc, -S(O)alquilo, -SO2alquilo, -SO2-haloalquilo, - SO2NRbRc, arilo, heteroarilo, cicloalquilo y heterocicloalquilo; en la que cada alquilo o alcoxi está sin sustituir o sustituido con -NRbRc, heterocicloalquilo, heteroarilo, o -C(O)alquilo; y cada arilo, heteroarilo, cicloalquilo y heterocicloalquilo está sin sustituir o sustituido con alquilo, halo, o -C(O)alquilo; (2) fenilo, cicloalquilo, heteroarilo, o heterocicloalquilo, cada uno sin sustituir o sustituido con uno o más sustituyentes seleccionados entre el grupo que consiste en alquilo, haloalquilo, hidroxi, -NRbRc, alcoxi, haloalcoxi, ciano, halo, oxo,-C(O)alquilo, -CO2alquilo, -C(O)-heterocicloalquilo, -CONRbRc, -S(O)alquilo, -SO2alquilo, -SO2-haloalquilo, -SO2NRbRc, arilo, heteroarilo, cicloalquilo y heterocicloalquilo; en la que cada alquilo o alcoxi está sin sustituir o sustituido con -NRbRc, heterocicloalquilo, heteroarilo, o -C(O)alquilo; y cada arilo, heteroarilo, cicloalquilo y heterocicloalquilo está sin sustituir o sustituido con alquilo, halo o -C(O)alquilo; o (3) -NkxRy, donde Rx es H o alquilo; y Ry es H, alquilo, alcoxialquilo, haloalquilo, -C(O)alquilo, -CO2alquilo, o -SO2alquilo; R2 y R3 son cada uno independientemente H o deuterio; y n es 1 o 2; o un estereoisómero del mismo, o una sal farmacéuticamente aceptable de tal compuesto o estereoisómero.
ES13755811.0T 2012-03-02 2013-03-01 Derivados de amidas y sulfonamidas amido espirocíclicas Active ES2620668T3 (es)

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US201261606291P 2012-03-02 2012-03-02
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PCT/CN2013/000216 WO2013127269A1 (en) 2012-03-02 2013-03-01 Amido spirocyclic amide and sulfonamide derivatives

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