AR101475A1 - PIRROLO DERIVATIVES [2,3-D] PYRIMIDINE - Google Patents

PIRROLO DERIVATIVES [2,3-D] PYRIMIDINE

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AR101475A1
AR101475A1 ARP150102546A ARP150102546A AR101475A1 AR 101475 A1 AR101475 A1 AR 101475A1 AR P150102546 A ARP150102546 A AR P150102546A AR P150102546 A ARP150102546 A AR P150102546A AR 101475 A1 AR101475 A1 AR 101475A1
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linear
branched alkyl
cycloalkyl
alkyl
branched
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ARP150102546A
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Spanish (es)
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Pfizer
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Abstract

En la presente, se describen derivados de pirrolo{2,3-d}pirimidina, su uso como inhibidores de la quinasa Janus (JAK), las composiciones farmacéuticas que los contienen y sus usos terapéuticos. Reivindicación 1: Un compuesto de la fórmula (1), o una sal de este aceptable desde el punto de vista farmacéutico, en donde R se selecciona de hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, C₁₋₆ perfluoroalquilo lineal o ramificado, arilo y alquilarilo; X se selecciona de --NH-- y --CRᵃRᵇ--, en donde (a) Rᵃ y Rᵇ son, independientemente, hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, C₃₋₆ cicloalquilo, arilo, (aril)C₁₋₆ alquilo lineal o ramificado, heteroarilo, (C₁₋₆ alquil lineal o ramificado)heteroarilo, (heteroaril)C₁₋₆ alquilo lineal o ramificado, (heterocíclico)C₁₋₆ alquilo lineal o ramificado, en donde el alquilo, arilo, heteroarilo y cicloalquilo pueden ser sustituidos opcionalmente con uno o más Rᶜ, o (b) Rᵃ y Rᵇ forman juntos una cadena que comprende --(CRᶜRᵈ)ʲ--, en donde Rᶜ y Rᵈ son, independientemente, hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, arilo, (C₁₋₆ alquil lineal o ramificado)arilo, heteroarilo, (C₁₋₆ alquil lineal o ramificado)heteroarilo, halo, CN, CF₃, hidroxilo, alcoxi, --CONH₂, --NHCO(C₁₋₆ alquilo), --CONH(C₁₋₆ alquilo), C₁₋₆ alcoxicarbonilo o SO₂CH₃; Y es -A-R¹, en donde A es un enlace, --NH--, --(CH₂)ₖ-- o --(CD₂)ₖ--, y R¹ es C₁₋₆ alquilo lineal o ramificado, C₃₋₆ cicloalquilo, arilo o --NRᵃRᵇ, o es una estructura de anillos monocíclicos o bicíclicos insaturados, saturados o parcialmente saturados que contiene un total de 4 a 11 átomos que tienen de 1 a 4 heteroátomos seleccionados independientemente del grupo que consiste en oxígeno, nitrógeno y azufre, en donde el alquilo, cicloalquilo, arilo o estructura de anillos monocíclicos o bicíclicos también se sustituyen opcionalmente con uno o más sustituyentes seleccionados independientemente del grupo que consiste en deuterio, halo, C₁₋₆ alquilo lineal o ramificado, C₃₋₆ cicloalquilo, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), (C₁₋₆ alcoxi lineal o ramificado)-O-(C₁₋₆ alquilo lineal o ramificado), CN, hidroxilo, CF₃, --ORᵉ, CO(C₁₋₆ alquilo lineal o ramificado), --CO(C₃₋₆ cicloalquilo), una estructura de anillos monocíclicos o bicíclicos insaturados, saturados o parcialmente saturados que contiene un total de 4 a 11 átomos como se definió anteriormente, --NRᵉRᶠ y --S(O)₂Rᵉ, y en donde el alquilo, alcoxi y cicloalquilo pueden ser sustituidos opcionalmente con uno o más sustituyentes seleccionados independientemente del grupo que consiste en C₁₋₆ alquilo lineal o ramificado, C₃₋₆ cicloalquilo, halo, CN, hidroxilo, --ORᵉ, CONH₂ y SO₂CH₃, en donde (a) Rᵃ y Rᵇ son, independientemente, hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, C₁₋₆ alcoxi lineal o ramificado-(C₁₋₆ alquilo lineal ramificado)--, C₃₋₆ cicloalquilo, arilo, (aril)C₁₋₆ alquilo lineal o ramificado, heteroarilo, heterocíclico, (C₁₋₆ alquil lineal o ramificado)heteroarilo, (heteroaril)C₁₋₆ alquilo lineal o ramificado, (heterocíclico)C₁₋₆ alquilo lineal o ramificado, en donde el alquilo, arilo, heteroarilo y cicloalquilo pueden ser sustituidos opcionalmente con uno o más Rᶜ; o (b) Rᵃ y Rᵇ forman juntos una cadena que comprende --(CRᶜRᵈ)ʲ--, en donde Rᶜ y Rᵈ son, independientemente, hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, C₁₋₆ alcoxi lineal o ramificado-(C₁₋₆ alquilo lineal o ramificado)--, C₃₋₆ cicloalquilo, arilo, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), (C₁₋₆ alquil lineal o ramificado)arilo, heteroarilo, (C₁₋₆ alquil lineal o ramificado)heteroarilo, halo, CN, hidroxilo, CF₃, --NHCO(alquilo), --CONH(alquilo), alcoxicarbonilo, CONH₂, --ORᵉ, --NRᵉRᶠ o --S(O)₂Rᵉ, en donde cualquier porción alquilo, cicloalquilo o alcoxi puede ser sustituida opcionalmente con uno o más átomos de halógeno; o (c) Rᵃ y Rᵇ forman juntos una cadena que comprende 4 a 6 átomos que tienen 1 ó 2 heteroátomos seleccionados independientemente de nitrógeno, oxígeno y azufre, en donde cualquier átomo de carbono puede ser sustituido opcionalmente con un sustituyente seleccionado del grupo que consiste en C₁₋₆ alquilo lineal o ramificado, C₃₋₆ cicloalquilo, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), C₁₋₆ alcoxi lineal o ramificado-(C₁₋₆ alquilo lineal o ramificado)--, arilo, (C₁₋₆ alquil lineal o ramificado)arilo, heteroarilo, (C₁₋₆ alquil lineal o ramificado)heteroarilo, heterocíclico, halo, CN, hidroxilo, CF₃, --NHCO(C₁₋₆ alquilo lineal o ramificado), --CONH(C₁₋₆ alquilo lineal o ramificado), C₁₋₆ alcoxicarbonilo lineal o ramificado, CONH₂, --ORᵉ, --NRᵉRᶠ o --S(O)₂Rᵉ, en donde cualquiera de las porciones alquilo, alcoxi o cicloalquilo puede ser sustituida opcionalmente con uno o más átomos de halógeno, y cualquier átomo de nitrógeno, si es químicamente aceptable, puede ser sustituido opcionalmente con C₁₋₆ alquilo lineal o ramificado, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), C₃₋₆ cicloalquilo, arilo, (C₁₋₆ alquil lineal o ramificado)arilo, -C(O)C₁₋₆ alquilo lineal o ramificado, -CONH(C₁₋₆ alquilo lineal o ramificado), C₁₋₆ alcoxicarbonilo, CONH₂ o --S(O)₂Rᵉ, en donde cualquiera de las porciones alquilo o cicloalquilo puede ser sustituida opcionalmente con uno o más átomos de halógeno; o (d) Rᵃ y Rᵇ forman juntos un anillo de bicicloalquilo de 5 a 10 miembros, en donde cualquier átomo del anillo puede ser sustituido opcionalmente con un sustituyente seleccionado del grupo que consiste en C₁₋₆ alquilo lineal o ramificado, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), C₃₋₆ cicloalquilo, C₁₋₆ alcoxi lineal o ramificado-(C₃₋₆ cicloalquilo), arilo, (C₁₋₆ alquil lineal o ramificado) arilo, heteroarilo, (C₁₋₆ alquil lineal o ramificado) heteroarilo, heterocíclico, halo, CN, hidroxilo, CF₃, --NHCO(C₁₋₆ alquilo lineal o ramificado), --CONH(C₁₋₆ alquilo lineal o ramificado), C₁₋₆ alcoxicarbonilo lineal o ramificado, CONH₂, --ORᵉ, --NRᵉRᶠ o --S(O)₂Rᵉ, en donde cualquiera de las porciones alquilo, alcoxi o cicloalquilo pueden ser sustituidas opcionalmente con uno o más átomos de halógeno; en donde Rᵉ y Rᶠ son, independientemente, hidrógeno, deuterio, C₁₋₆ alquilo lineal o ramificado, C₁₋₆ alcoxi o C₃₋₆ cicloalquilo, en donde el alquilo y cicloalquilo pueden ser sustituidos opcionalmente con uno o más sustituyentes seleccionados independientemente del grupo que consiste en halo, CN, hidroxilo, C₁₋₆ haloalquilo lineal o ramificado y CONH₂; y, j es 2, 3, 4 ó 5; y k es 0, 1, 2, 3, ó 4.Herein, derivatives of pyrrolo {2,3-d} pyrimidine, their use as Janus kinase inhibitors (JAK), the pharmaceutical compositions containing them and their therapeutic uses are described. Claim 1: A compound of the formula (1), or a pharmaceutically acceptable salt thereof, wherein R is selected from hydrogen, deuterium, C₁₋₆ linear or branched alkyl, C₁₋₆ linear or branched perfluoroalkyl , aryl and alkylaryl; X is selected from --NH-- and --CRᵃRᵇ--, where (a) Rᵃ and Rᵇ are, independently, hydrogen, deuterium, C₁₋₆ linear or branched alkyl, C₃₋₆ cycloalkyl, aryl, (aryl) C₁₋₆ linear or branched alkyl, heteroaryl, (C₁₋₆ linear or branched alkyl) heteroaryl, (heteroaryl) C₁₋₆ linear or branched alkyl, (heterocyclic) C₁₋₆ linear or branched alkyl, wherein the alkyl, aryl, heteroaryl and cycloalkyl can be optionally substituted with one or more Rᶜ, or (b) Rᵃ and Rᵇ together form a chain comprising - (CRᶜRᵈ) ʲ--, where Rᶜ and Rᵈ are, independently, hydrogen, deuterium, C₁₋ ₆ linear or branched alkyl, aryl, (C₁₋₆ linear or branched alkyl) aryl, heteroaryl, (C₁₋₆ linear or branched alkyl) heteroaryl, halo, CN, CF₃, hydroxyl, alkoxy, --CONH₂, --NHCO ( C₁₋₆ alkyl), --CONH (C₁₋₆ alkyl), C₁₋₆ alkoxycarbonyl or SO₂CH₃; Y is -A-R¹, where A is a bond, --NH--, - (CH₂) ₖ-- or - (CD₂) ₖ--, and R¹ is C₁₋₆ linear or branched alkyl, C₃ ₋₆ cycloalkyl, aryl or --NRᵃRᵇ, or is an unsaturated, saturated or partially saturated monocyclic or bicyclic ring structure containing a total of 4 to 11 atoms having 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, wherein the alkyl, cycloalkyl, aryl or monocyclic or bicyclic ring structure is also optionally substituted with one or more substituents independently selected from the group consisting of deuterium, halo, C₁₋₆ linear or branched alkyl, C₃₋₆ cycloalkyl, C₁₋₆ linear or branched alkoxy- (C₃₋₆ cycloalkyl), (C₁₋₆ linear or branched alkoxy) -O- (C₁₋₆ linear or branched alkyl), CN, hydroxyl, CF₃, --ORᵉ, CO (C₁₋₆ linear or branched alkyl), --CO (C₃₋₆ cycloalkyl), or A structure of unsaturated, saturated or partially saturated monocyclic or bicyclic rings containing a total of 4 to 11 atoms as defined above, --NRᵉRᶠ and --S (O) ₂Rᵉ, and wherein the alkyl, alkoxy and cycloalkyl may be optionally substituted with one or more substituents independently selected from the group consisting of C₁₋₆ linear or branched alkyl, C₃₋₆ cycloalkyl, halo, CN, hydroxyl, --ORᵉ, CONH₂ and SO₂CH₃, where (a) Rᵃ and Rᵇ are , independently, hydrogen, deuterium, C₁₋₆ linear or branched alkyl, C₁₋₆ linear or branched alkoxy- (C₁₋₆ branched linear alkyl) -, C₃₋₆ cycloalkyl, aryl, (aryl) C₁₋₆ linear alkyl or branched, heteroaryl, heterocyclic, (C₁₋₆ linear or branched alkyl) heteroaryl, (heteroaryl) C₁₋₆ linear or branched alkyl, (heterocyclic) C₁₋₆ linear or branched alkyl, wherein the alkyl, aryl, heteroaryl and cycloalkyl it can be optionally substituted with one or more Rᶜ; or (b) Rᵃ and Rᵇ together form a chain comprising - (CRᶜRᵈ) ʲ--, where Rᶜ and Rᵈ are, independently, hydrogen, deuterium, C₁₋₆ linear or branched alkyl, C₁₋₆ linear or branched alkoxy - (C₁₋₆ linear or branched alkyl) -, C₃₋₆ cycloalkyl, aryl, C₁₋₆ linear or branched alkoxy- (C₃₋₆ cycloalkyl), (C₁₋₆ linear or branched alkyl) aryl, heteroaryl, (C₁ ₋₆ linear or branched alkyl) heteroaryl, halo, CN, hydroxyl, CF₃, --NHCO (alkyl), --CONH (alkyl), alkoxycarbonyl, CONH₂, --ORᵉ, --NRᵉRᶠ or --S (O) ₂Rᵉ , wherein any alkyl, cycloalkyl or alkoxy portion may be optionally substituted with one or more halogen atoms; or (c) Rᵃ and Rᵇ together form a chain comprising 4 to 6 atoms having 1 or 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein any carbon atom can be optionally substituted with a substituent selected from the group consisting of in C₁₋₆ linear or branched alkyl, C₃₋₆ cycloalkyl, C₁₋₆ linear or branched alkoxy- (C₃₋₆ cycloalkyl), C₁₋₆ linear or branched alkoxy- (C₁₋₆ linear or branched alkyl) -, aryl , (C₁₋₆ linear or branched alkyl) aryl, heteroaryl, (C₁₋₆ linear or branched alkyl) heteroaryl, heterocyclic, halo, CN, hydroxyl, CF₃, --NHCO (C₁₋₆ linear or branched alkyl), - CONH (C₁₋₆ linear or branched alkyl), C₁₋₆ linear or branched alkoxycarbonyl, CONH₂, --ORᵉ, --NRᵉRᶠ or --S (O) ₂Rᵉ, wherein any of the alkyl, alkoxy or cycloalkyl portions may be optionally substituted with one or more halo atoms Gene, and any nitrogen atom, if chemically acceptable, can be optionally substituted with C₁₋₆ linear or branched alkyl, C₁₋₆ linear or branched alkoxy- (C₃₋₆ cycloalkyl), C₃₋₆ cycloalkyl, aryl, (C₁ ₋₆ linear or branched alkyl) aryl, -C (O) C₁₋₆ linear or branched alkyl, -CONH (C₁₋₆ linear or branched alkyl), C₁₋₆ alkoxycarbonyl, CONH₂ or --S (O) ₂Rᵉ, in wherein any of the alkyl or cycloalkyl moieties may be optionally substituted with one or more halogen atoms; or (d) Rᵃ and Rᵇ together form a 5 to 10 membered bicycloalkyl ring, wherein any atom of the ring can be optionally substituted with a substituent selected from the group consisting of C₁₋₆ linear or branched alkyl, C₁₋₆ alkoxy linear or branched- (C₃₋₆ cycloalkyl), C₃₋₆ cycloalkyl, C₁₋₆ linear or branched alkoxy- (C₃₋₆ cycloalkyl), aryl, (C₁₋₆ linear or branched alkyl) aryl, heteroaryl, (C₁₋₆ linear or branched alkyl) heteroaryl, heterocyclic, halo, CN, hydroxyl, CF₃, --NHCO (C₁₋₆ linear or branched alkyl), --CONH (C₁₋₆ linear or branched alkyl), C₁₋₆ linear or branched alkoxycarbonyl , CONH₂, --ORᵉ, --NRᵉRᶠ or --S (O) ₂Rᵉ, wherein any of the alkyl, alkoxy or cycloalkyl moieties may be optionally substituted with one or more halogen atoms; wherein Rᵉ and Rᶠ are independently hydrogen, deuterium, C₁₋₆ linear or branched alkyl, C₁₋₆ alkoxy or C₃₋₆ cycloalkyl, wherein the alkyl and cycloalkyl can be optionally substituted with one or more substituents independently selected from the group consisting of halo, CN, hydroxyl, C₁₋₆ linear or branched haloalkyl and CONH₂; and, j is 2, 3, 4 or 5; and k is 0, 1, 2, 3, or 4.

ARP150102546A 2014-08-12 2015-08-07 PIRROLO DERIVATIVES [2,3-D] PYRIMIDINE AR101475A1 (en)

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