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ES2555491T3 - Composiciones y métodos para la inhibición de la ruta de JAK - Google Patents

Composiciones y métodos para la inhibición de la ruta de JAK Download PDF

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Publication number
ES2555491T3
ES2555491T3 ES10701189.2T ES10701189T ES2555491T3 ES 2555491 T3 ES2555491 T3 ES 2555491T3 ES 10701189 T ES10701189 T ES 10701189T ES 2555491 T3 ES2555491 T3 ES 2555491T3
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Spain
Prior art keywords
ylamino
methyl
oxo
methylpyrimidin
pyrimidin
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ES10701189.2T
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English (en)
Inventor
Hui Li
Thilo J. Heckrodt
Yan Chen
Darren John Mcmurtrie
Vanessa Taylor
Rajinder Singh
Pingyu Ding
Sambaiah Thota
Rose Yen
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Rigel Pharmaceuticals Inc
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Rigel Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

Un compuesto de formula I:**Fórmula** o una sal del mismo, en el que: X e Y son cada uno independientemente O, S, S(O), SO2 o NR1; cada R1 es independientemente para cada aparición H, alquilo C1-6 opcionalmente sustituido, C(O)-alquilo C1-6, CO2- alquilo C1-6 o R50; cada R50 es C(R9)2-O-R10 o C(R9)2-S-R10; cada R9 es independientemente para cada aparición H, alquilo C1-6 opcionalmente sustituido, arilo C6-10 opcionalmente sustituido o arilalquilo C7-16 opcionalmente sustituido; o como alternativa, dos R9, junto con el carbono al que están unidos, forman un grupo cicloalquilo C3-8 opcionalmente sustituido o un heteroarilciclilo de 3-8 miembros opcionalmente sustituido 3-8; R10 es Ra o -P(O)(OR11)2; cada R11 es independientemente para cada aparición Ra o un grupo catiónico monovalente; o dos R11, junto con los átomos a los que están unidos, forman un grupo fosfato cíclico de 4-8 miembros, o dos R11 juntos representan un grupo catiónico divalente; el anillo A es un arilo C6-10 o un heteroarilo de 5-10 miembros; cada R2 es independientemente para cada aparición H, Re, Rb, Re sustituido con uno o más de los mismos o diferentes Ra y/o Rb, -ORe sustituido con uno o más de los mismos o diferentes Ra y/o Rb, -SRe sustituido con uno o más de los mismos o diferentes Ra y/o Rb, -C(O)Re sustituido con uno o más de los mismos o diferentes Ra y/o Rb, - N(Ra)Re en el que Re está sustituido con uno o más de los mismos o diferentes Ra y/o Rb, -S(O)2Re sustituido con uno o más de los mismos o diferentes Ra y/o Rb, -B(ORa)2, -B(N(Rc)2)2, -(C(Ra)2)m-Rb, -O-(C(Ra)2)m-Rb, -S-(C(Ra)2)m- Rb, -O-(C(Rb)2)m-Ra, -N(Ra)-(C(Ra)2)m-Rb, -O-(CH2)m-CH((CH2)mRb)Rb, -C(O)N(Ra)-(C(Ra)2)m-Rb, -O-(C(Ra)2)m- C(O)N(Ra)-(C(Ra)2)m-Rb,-N((C(Ra)2)mRb)2, -S-(C(Ra)2)m-C(O)N(Ra)-(C(Ra)2)m-Rb, -N(Ra)-C(O)-N(Ra) -(C(Ra)2)m-Rb25 , - N(Ra)-C(O)-(C(Ra)2)m-C(Ra)(Rb)2 o -N(Ra)-(C(Ra)2)m-C(O)-N(Ra)-(C(Ra)2)m-Rb; cada Ra es independientemente para cada aparición H, deuterio, alquilo C1-6, cicloalquilo C3-8, cicloalquilalquilo C4-11, arilo C6-10, arilalquilo C7-16, heteroalquilo de 2-6 miembros, heteroaliciclilo de 3-10 miembros, heteroaliciclilalquilo de 4-11 miembros, heteroarilo 5-15 miembros o heteroarilalquilo de 6-16 miembros; cada Rb es independientemente para cada aparición >=O, -ORa, -O-(C(Ra)2)m,-ORa, haloalquiloxi C1-3, >=S, -SRa, >=NRa, >=NORa, -N(Rc)2, halo, -CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, >=N2, -N3, -S(O)Ra, -S(O)2Ra, -SO3Ra, - S(O)N(Rc)2, -OS(O)Ra, -OS(O)2Ra, -OSO3Ra, -OS(O)2N(Rc)2, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2, -C(NRa)-N(Rc)2, - C(NOH)-Ra, -C(NOH)-N(Rc)2, -OC(O)Ra, -OC(O)ORa, -OC(O)N(Rc)2, -OC(NH)-N(Rc)2, -OC(NRa)-N(Rc)2, - [N(Ra)C(O)]nRa, -[N(Ra)C(O)]nORa, -[N(Ra)C(O)]nN(Rc)2 o -[N(Ra)C(NRa)]n-N(Rc)2; cada Rc es independientemente para cada aparición Ra, o, como alternativa, se toman juntos dos Rc con el átomo de nitrógeno al que se enlazan para formar un heteroaliciclilo de 3 a 10 miembros o un heteroarilo de 5-10 miembros que opcionalmente puede incluir uno o más de los mismos o diferentes heteroátomos adicionales y que está opcionalmente sustituido con uno o más de los mismos o diferentes grupos Ra y/o Rd; cada Rd es >=O, -ORa, halo alquiloxi C1-3,alquilo C1-6, >=S, -SRa, >=NRa, >=NORa, -N(Ra)2, halo, -CF3, -CN, -NC, -OCN, - SCN, -NO, -NO2, >=N2, -N3, -S(O)Ra, -S(O2)Ra, -SO3Ra, -S(O)N(Ra)2, -S(O)2N(Ra)2, -OS(O)Ra, -OS(O)2Ra, -OSO3Ra, - OS(O)2N(Ra)2, -C(O)Ra, -CO2Ra, -C(O)N(Ra)2, -C(NRa)N(Ra)2, -C(NOH)Ra, -C(NOH)N(Ra)2, -OCO2Ra, -OC(O)N(Ra)2, -OC(NRa)N(Ra)2 -[N(Ra)C(O)]nRa, -(C(Ra)2)n-ORa, -N(Ra)-S(O)2Ra, -C(O)-haloalquilo C1-6, -S(O)2- haloalquilo C1-6, - OC(O)Ra, -O(C(Ra)2)m-ORa, -S(C(Ra)2)m-ORa, -N(Ra)-haloalquilo C1-6, -P(O)(ORa)2, -N(Ra)-(C(Ra)2)m-ORa, - [N(Ra)C(O)]nORa, -[N(Ra)C(O)]nN(Ra)2, -[N(Ra)C(NRa)]n(Ra)2 o -N(Ra)C(O)-haloalquilo C1-6; o dos Rd, tomados junto con el átomo o átomos a los que están unidos, se combinan para formar un anillo mono o bicíclico, parcial o totalmente saturado de 3-10 miembros, que contiene opcionalmente uno o más heteroátomos y está opcionalmente sustituido con uno o más Ra; cada Re es independientemente para cada aparición alquilo C1-6, cicloalquilo C3-8, cicloalquilalquilo C4-11, arilo C6-10, arilalcilo C7-16, heteroalquilo de 2-6 miembros, heteroaliciclilo de 3-10 miembros, heteroaliciclilalquilo de 4-11 miembros, heteroarilo de 5-15 miembros o heteroarilalquilo de 6-16 miembros; p es 0, 1, 2, 3 o 4; cada m es 1, 2 o 3; cada n es 0, 1,2 o 3; o dos grupos R2, tomados junto con el átomo o átomos a los que están unidos, se combinan para formar un anillo mono o bicíclico, parcial o totalmente saturado de 4-10 miembros, que contiene opcionalmente uno o más heteroátomos y está opcionalmente sustituido con uno o más Ra y/o Rb; Z1 y Z2 son cada uno independientemente CH, CR2 o N; R3 es H, alquilo C1-6 opcionalmente sustituido o R50; R4 es H, alquilo C1-6 opcionalmente sustituido o R50; y R5 es halo, -CN, alquilo C1-6 opcionalmente sustituido, alquinilo, hidroxi, alcoxi C1-6 opcionalmente sustituido, nitro, - N(Ra)2, -C(O)N(Ra)2, -CO2Ra o -C(O)Ra.

Description

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CF3, -CN, -S(O)2N(Rc)2, -S(O)2Ra, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2, -C(Ra)2-N(Rc)2 o -[N(Ra)C(O)]nRa; y uno de R2a y R2b no sea H. En otra realización, cada uno de R2a y R2b es H, alquilo C1-6, -ORa, -OCF3, halo, -N(Rc)2, -CF3, -C(Ra)2N(Rc)2 o -CN. En otra realización, R2b es -CF3 o -CH3; y R2a es halo o -CH3. En otra realización, R2a es H, -CH3, -CF3, -ORa o -OCF3; y R2b es -N(Rc)2 o -C(Ra)2-N(Rc)2. En otra realización más, R2a es -N(Rc)2 o -C(Ra)2-N(Rc)2; y R2b es H, -CH3, -CF3, -ORa o -OCF3.
Aún en otra realización es un compuesto de fórmulas estructurales IA1 o IA2, en las que R2c y R2d son H, y R5 es F o CH3; R2a y R2b se toman junto con los carbonos a los que están unidos para formar un anillo mono o bicíclico, parcial
o totalmente saturado de 4-10 miembros, que contiene opcionalmente uno o más heteroátomos y opcionalmente sustituido con uno o más Ra y/o Rb. En una realización, este es un anillo de 5 miembros, y en una realización más específica el anillo de 5 miembros es ciclopentano, pirrolidina, imidazolidina, 1,3-dioxolano, oxazolidina o tetrahidrofurano; opcionalmente sustituido con uno o más Ra y/o Rb. En una realización específica, el anillo de 5 miembros es pirrolidina, y en una realización incluso más específica los compuestos están de acuerdo con fórmula IA3:
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en la que Rb es OH, alquilo C1-6, -CO2-alquilo C1-6, -C(O)-alquilo C1-6 o -S(O)2-alquilo C1-6. En otra realización, R2a y R2b se toman junto con los carbonos a los que están unidos para formar un anillo monocíclico parcial o totalmente saturado de 6, 7 u 8 miembros, que contiene opcionalmente uno o más heteroátomos y opcionalmente sustituido con uno o más Ra y/o Rb. En una realización, cuando el anillo es de 6 miembros, el anillo es ciclohexano, morfolina, piperidina, dioxano, oxatiazinano o piperazina; opcionalmente sustituido con uno o más Ra y/o Rb. En otra realización, cuando el anillo es de 7 miembros, el anillo es cicloheptano, ciclohepteno, azepano, tetrahidroazepina o diazepano; opcionalmente sustituido con uno o más Ra y/o Rb. En otra realización más, cuando el anillo es de 8 miembros, el anillo es ciclooctano, cicloocteno, azocano, hexahidroazocina, diazocano o hexahidrodiazocina; opcionalmente sustituido con uno o más Ra y/o Rb. Para cada una de las realizaciones anteriores, en las que R2a y R2b se toman junto con los carbonos a los que están unidos para formar un anillo monocíclico parcial o totalmente saturado de 5, 6, 7 u 8 miembros, hay una realización más específica en la que hay 0, 1, 2 o 3 en cada uno de Ra y Rb, y Ra es alquilo C1-6; y cada Rb es independientemente para cada aparición =O, -ORa, haloalquiloxi C1-3, -SRa, N(Rc)2, halo, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2 o -C(Ra)2-N(Rc)2. Por ejemplo, en una realización, hay al menos un Rb que es =O; y opcionalmente un Ra que es alquilo C1-6 opcionalmente sustituido. Ejemplos particulares de compuestos de acuerdo con la fórmula IA3, incluyen, pero sin limitación, se abarcan compuestos tales como IV-2, IV-10, IV-14 a través de IV-16, IV-18 a través de IV-34 y IV-50 (véase Tabla IV).
Algunas realizaciones incluyen compuestos en los que el anillo A es otro distinto de fenilo. En una realización específica, el anillo A es piridina o piridazina. Como se muestra en la fórmula I, y con respecto a esta realización, la piridina o piridazina puede tener diversas configuraciones regioquímicas y puntos de unión a la molécula precursora.
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en los que las variables de definen de la misma manera como para los de fórmula I, y además: Q1 y Q2 son cada uno independientemente N o CR2, con la condición de que al menos uno de Q1 y Q2 sea N; X e Y son cada uno independientemente O o NR1; cada R1 es independientemente para cada aparición H, alquilo C1-6 opcionalmente sustituido o R50; p es 0, 1, 2 o 3; y R5 es halo, -CN, alquilo C1-6 opcionalmente sustituido, nitro, -N(Ra)2, -C(O)N(Ra)2, -CO2Ra o -C(O)Ra.
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en la que cada uno de R2a, R2b, R2c y R2d (cuando están presentes) es independientemente para cada aparición como se define para R2
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Una realización es un compuesto de fórmula estructural IB1 o IB2, en la que X e Y son cada uno independientemente NR1. En una realización más específica, X e Y son cada uno independientemente NH o Nalquilo C1-6. EN una realización incluso más específica, X e Y son cada uno independientemente NH o NCH3. En una realización, en la que X e Y se definen más específicamente como se han mencionado, R5 es halo o alquilo C1-6; Z1 es CH, C-Halo o C-alquilo C1-6 opcionalmente sustituido; y Z2 es CH. En otra realización, R2a y R2d son H; y R5 es F o CH3. En otra realización, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -ORa, -OCH2F, -OCF3, -SRa, -N(Rc)2, halo, -OCF2H, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2, -C(Ra)2-N(Rc)2 o [N(Ra)C(O)]nRa; y uno de R2b y R2c no es H. En tal otra realización, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -N(Rc)2, halo, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2, o -C(Ra)2N(Rc)2. En otra realización, R2b es H, halo, -CF3, -CN o -CH3; y RZc es -N(Rc)2, -S(O)2Ra, -C(O)N(Rc)2 o -C(Ra)2N(Rc)2.
Otra realización es un compuesto de fórmula estructural IB1 o IB2, en la que X es O e Y es NR1. En una realización, R5 es halo o alquilo C1-6; Z1 es CH, C-Halo o C-alquilo C1-6 opcionalmente sustituido; y Z2 es CH. En otra realización, R2a y R2d son H; y R5 es F o CH3. En una realización más específica, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -ORa, -OCF3, -SRa, -N(Rc)2, halo, -OCF2H, -OCH2F, -CF3, -CN, -S(O)2Ra, C(O)Ra, -CO2Ra, -C(O)N(Rc)2, -C(Ra)2-N(Rc)2 o -[N(Ra)C(O)nNRa; y uno de R2b y R2c no es H. En otra realización, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -N(Rc)2, halo, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, -C(O)N(Rc)2, o -C(Ra)2-N(Rc)2. En una realización más específica R2b es H, halo, -CF3, -CN o -CH3; y R2c es -N(Rc)2, -S(O)2Ra, -C(O)N(Rc)2 o -C(Ra)2-N(Rc)2. En otra realización, R2b es H, halo, -CF3, -CN o -CH3; y R2c es -N(Rc)2 o -C(Ra)2-N(Rc)2.
Otra realización es un compuesto de fórmula estructural IB1 o IB2, en la que X es O; Y es NR1; Z1 es CH, C-Halo o C-alquilo C1-6 opcionalmente sustituido; Z2 es CH; R2a y R2d son H; y R5 es F o CH3, R2b y R2c se toman junto con los carbonos a los que están unidos para formar un anillo mono o bicíclico, parcial o totalmente saturado de 4-10 miembros, que contiene opcionalmente uno o más heteroátomos y opcionalmente sustituido con uno o más Ra y/o Rb. En una realización, el anillo es un anillo monocíclico, parcial o totalmente saturado de 5, 6, 7 u 8 miembros opcionalmente sustituido con uno o más Ra y/o Rb. En una realización, el anillo monocíclico, saturado de 5, 6, 7 u 8 miembros es ciclopentano, pirrolidina, imidazolidina, 1,3-dioxolano, oxazolidina, tetrahidrofurano, ciclohexano, morfolina, piperidina, dioxano, oxatiazinano, piperazina, cicloheptano, ciclohepteno, azepano, tetrahidroazepina, diazepano, ciclooctano, cicloocteno, azocano, hexahidroazocina, diazocano o hexahidrodiazocina; opcionalmente sustituido con uno o más Ra y/o Rb. Para cada uno de las realizaciones anteriores, en las que R2b y R2c se toman junto con los carbonos a los que están unidos para formar un anillo monocíclico, saturado de 5, 6, 7 u 8 miembros, hay una realización más específica en la que hay 0, 1, 2 o 3 cada uno de Ra y Rb, y Ra es alquilo C1-6; y cada Rb es independientemente para cada aparición =O, -ORa, haloalquiloxi C1-3, -SRa, -N(Rc)2, halo, -CF3, -CN, -S(O)2Ra, C(O)Ra, -CO2Ra, -C(O)N(Rc)2, o -C(Ra)2-N(Rc)2. Por ejemplo, en una realización, hay al menos un Rb que es =O; y opcionalmente un Ra que es alquilo C1-6 opcionalmente sustituido. En esta realización se abarcan compuestos tales como IV-45, IV-46 y IV-47 (véase Tabla IV).
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Una realización es un compuesto de fórmula estructural IB3, en la que X es O e Y es NR1. En una realización, R5 es halo o alquilo C1-6; Z1 es CH, C-Halo o C-alquilo C1-6 opcionalmente sustituido; y Z2 es CH. En otra realización, R2a es H; y R5 es F o CH3. En una realización más específica, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -ORa, -OCF3, -SRa, -N(Rc)2, halo, -OCF2H, -OCH2F, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, C(O)N(Rc)2, -C(Ra)2-N(Rc)2 o -[N(Ra)C(O)]nRa; y uno de R2b y R2c no es H. En otra realización, cada uno de R2b y R2c es independientemente para cada aparición H, alquilo C1-6, -N(Rc)2, halo, -CF3, -CN, -S(O)2Ra, -C(O)Ra, -CO2Ra, C(O)N(Rc)2, o -C(Ra)2-N(Rc)2. En una realización más específica R2b es H, halo, -CF3, -CN o -CH3; y R2c es -N(Rc)2, S(O)2Ra, -C(O)N(Rc)2 o -C(Ra)2-N(Rc)2. En otra realización, R2b es H, halo, -CF3, -CN o -CH3; y R2c es -N(Rc)2 o C(Ra)2-N(Rc)2.
Otra realización es un compuesto de fórmula estructural IB3, en la que X es O; Y es NR1; Z1 es CH, C-Halo o Calquilo C1-6 opcionalmente sustituido; Z2 es CH; R2c y R2d son H; y R5 es F o CH3, R2b y R2c se toman junto con los carbonos a los que están unidos para formar un anillo mono o bicíclico, parcial o totalmente saturado de 4-10 miembros, que contiene opcionalmente uno o más heteroátomos y opcionalmente sustituido con uno o más Ra y/o Rb. En una realización, el anillo es un anillo monocíclico parcial o totalmente saturado de 5, 6, 7 u 8 miembros
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Tabla II
Cpd
X Y Z1 R5 R2a R2b R2c R2d
II-1
O NH CH CH3 H H -N(CH3)2 H
II-2
O NH CH CH3 H H H
II-3
O NH CH CH3 H H 1-metil-1,4-diazepan-4-ilo H
II-4
O N-(n-propil) CH CH3 H H 1-metilpiperazin-4-ilo H
II-5
O N-(n-propil) CH CH3 H H imagen44 H
II-6
O NH CH CH3 H H 4-metilpiperidin-1-ilo H
II-7
O N-(isopropil) CH CH3 H H 1-metilpiperazin-4-ilo H
II-8
O NH CH CH3 H H imagen44 H
II-9
O NH CH CH3 H H H
II-10
O NH CH CH3 H H piperazin-1-ilo H
II-11
O NH CH CH3 H H imagen45 H
II-12
O NH CH CH3 H H H
II-13
O NH CH CH3 H H 1-metilpiperazin-4-ilo H
II-14
O NH CH F H H 1-metilpiperazin-4-ilo H
II-15
NH NH CH CH3 H H 1-metilpiperazin-4-ilo H
II-16
NH NH CH F H H 1-metilpiperazin-4-ilo H
II-17
O NH CH CH3 H H morfolin-4-ilo H
II-18
O NH CH F H H morfolin-4-ilo H
II-19
NH NH CH F H H morfolin-4-ilo H
II-20
NCH3 NCH3 CH CH3 H H 1-metilpiperazin-4-ilo H
II-21
NCH3 NCH3 CH F H H 1 -metilpiperazin-4-ilo H
II-22
O NCH3 CH CH3 H H 1-metilpiperazin-4-ilo H
II-23
NCH3 O CH CH3 H H 1-metilpiperazin-4-ilo H
II-24
O NCH3 CH F H H 1-metilpiperazin-4-ilo H
II-25
NH O CH CH3 H H 1-metilpiperazin-4-ilo H
II-26
O NH CH CH3 H CH3 1-metilpiperazin-4-ilo H
II-27
NH NH CH CH3 H CH3 1-metilpiperazin-4-ilo H
II-28
O NH CH CH3 H CH3 H
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II-29
O NH CH F H CH3 H
II-30
O NH CH F H CH3 1-metilpiperazin-4-ilo H
II-31
O NH CH CH3 H H H
II-32
O NH CH CH3 H H H
II-33
O NH CH F H H H
II-34
O NH CH F H H H
II-35
O NH CH CH3 H H -N(H)-1-metilpiperidin-4-ilo H
II-36
O NH CH CH3 H H -N(H)-piperidin-4-ilo H
II-37
O NH CH CH3 H H H
II-38
O NH CH CH3 H H H
II-39
O NH CH CH3 H CF 3 1-metilpiperazin-4-ilo H
II-40
O NH CH CH3 H F H
II-41
O NH CH CH3 H H H
II-42
O NH CH CH3 H H H H
II-43
O NH CH CH3 H H S(O)2CH3 H
II-44
O NH CH CH3 H H H
II-45
O NH CH CH3 H H -C(O)-piperazin-1-ilo H
II-46
O NH CH CH3 H H H
II-47
O NH CH CH3 H H H
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II-48
O NH CH CH3 H F H
II-49
O NH CH CH3 H F H
II-50
O NH CH CH3 H F H
II-51
O NH CH CH3 H F H
II-52
O NH CH CH3 H F H
II-53
O NH CH CH3 H F H
II-54
O NH CH CH3 H F H
II-55
O NH CH CH3 H H H
II-56
O NH CH CH3 H H H
II-57
O NH CH CH3 H H H
II-58
O NH CH CH3 H H H
II-59
O NH CH CH3 H H 4,4-difluoropiperidin-1-ilo H
II-60
O NH CH CH3 H H 4,4-dimetilpiperidin-1-ilo H
II-61
O NH CH CH3 H CH3 imagen44 H
II-62
O NH CH CH3 H CH3 H
II-63
O NH CH CH3 H CH3 H
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II-64
O NH CH CH3 H CH3 H
II-65
O NH CH CH3 H CH3 H
II-66
O NH CH CH3 H CH3 H
II-67
O NH CH CH3 H CH3 imagen44 H
II-68
O NH CH CH3 H CH3 H
II-69
O NH CH CH3 H CH3 H
II-70
O NH CH CH3 H H H
II-71
O NH CH CH3 H H pirrolidin-1-ilo H
II-72
O NH CCH3 CH3 H H 1-metilpiperazin-4-ilo H
II-73
O NH CCH3 CH3 H H morfolin-4-ilo H
II-74
O NH CH CH3 H H -N(H)CH2-ciclopropil H
II-75
O NH CF CH3 H H 1-metilpiperazin-4-ilo H
II-76
O NH CF CH3 H H morfolin-4-ilo H
II-77
O NH CH CH3 H Br H H
II-79
O NCH3 CH CH3 H H -N(H)S(O)2CH3 H
II-80
O NH CH CH3 H H H
II-81
O NH CH CH3 H H H
II-82
O NH CH CH3 H H H
II-83
O NH CH CH3 H H H
II-84
O NH CH CH3 H H H
II-85
O NH CH CF3 H H 1-metilpiperazin-4-ilo H
II-86
O NH CH CH3 H H H
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O NH CH CH3 H H H
11-88
O NH CH CH3 H H H
11-89
O NH CH CH3 H H imagen44 H
11-90
O NH CH CH3 H H H
11-91
O NH CH CH3 H H H
II-92
O NH CH CH3 H H H
II-94
O NH CH CH3 H H H
II-95
O NH CH CH3 H H H
II-96
O NH CH CH3 H H H
II-97
O NH CH CH3 H H H
II-98
O NH CH CH3 H H H
II-99
O NH CH CH3 H H H
II-100
O NH CH CH3 H H imagen44 H
II-101
O NH CH CH3 H H H
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O NH CH CH3 H H H
II-103
O NH CH CH3 H H H
II-104
O NH CH CH3 H H H
II-105
O NH CH CH3 H H H
II-106
O NH CH CH3 H H imagen46 H
II-107
O NH CH CH3 H H H
II-108
O NH CH CH3 H H H
II-109
O NH CH CH3 H CF 3 imagen44 H
II-110
O NH CH CH3 H CF 3 1-etilpiperazin-4-ilo H
II-111
O NH CH CH3 H F 1-metilpiperazin-4-ilo H
II-112
O NH CH CH3 H F H
II-113
O NH CH CH3 H F H
II-114
O NH CH CH3 H F 1-etilpiperazin-4-ilo H
II-115
O NH CH CH3 H CN H
11-116
O NH CH CH3 H Cl 1 -metilpiperazin-4-ilo H
48
II-117
O NH CH CH3 H H H
11-118
O NH CH CH3 H Cl imagen44 H
II-119
O NH CH CH3 H CF 3 H
11-120
O NH CH CH3 H H imagen44 H
II-121
O NH CH CH3 H H H
II-122
O NH CH CH3 H Cl H
II-123
O NH CH CH3 H H -OCH3 H
II-124
O NH CH CH3 H CF3 imagen44 H
II-125
O NH CH CH3 H F H
II-126
O NH CH CH3 H H H
II-127
O NH CH CH3 H H H
II-128
O NH CH CH3 H H H
II-129
O NH CH CH3 H H imagen47 H
II-130
O NH CH CH3 H H H
II-131
O NH CH CH3 H H H
49
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O NH CH CH3 H H H
II-133
O NH CH CH3 H H H
II-134
O NH CH CH3 H H H
II-135
O NH CH CH3 H H imagen44 H
II-136
O NH CH CH3 H H 1-isopropilpiperazin-4-ilo H
II-137
O NH CH CH3 H H H
II-138
O NH CH CH3 H H H
II-139
O NH CH CH3 H H H
11-140
O NH CH CH3 H OCH3 OCH3 H
II-141
O NH CH CH3 H OCH3 OCH3 H
II-142
O NH CH CH3 H H OCH2CH2OH H
II-143
O NH CH CH3 CH3 H 1 -metilpiperazin-4-ilo H
II-144
O NH CH CH3 H H OCH(CH3)2 H
II-145
O NH CH CH3 H H OCH2CH2OCH3 H
11-146
O NH CH CH3 H H OC(CH3)2C(O)NH2 H
II-147
O NH CH CH3 H CF 3 OCH3 H
11-148
O NH CH CH3 H H OCH2CH2CH2OH H
II-149
O NH CH CH3 H H OCH2CH2CH2OCH3 H
II-150
O NH CH CH3 H Cl H
II-151
O NH CH CH3 H H H
II-152
O NH CH CH3 H OCH3 H H
II-153
O NH CH CH3 H CH3 CH3 H
50
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Claims (1)

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    I-65 N2-((3-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-6-il)-5-metilpirimidin-2,4-diamina; I-66 N2-((4-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-6-il)-5-metilpirimidin-2,4-diamina; I-69 N2-((3-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-5-il)-5-metilpirimidin-2,4-diamina; I-70 N2-((4-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-5-il)-5-metilpirimidin-2,4-diamina; I-77 N2-((3-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-5-il)-5-fluoropirimidin-2,4-diamina; I-78 N2-((4-metilsulfonil)fenil)-N4-(3-metil-2-oxo-2,3-dihidrobenzo[d]oxazol-5-il)-5-fluoropirimidin-2,4-diamina; I-100 N2-((3-metilsulfonil)fenil)-N4-(2-oxo-2,3-dihidrobenzo[d]oxazol-6-il)-5-metilpirimidin-2,4-diamina; I-101 N2-((4-metilsulfonil)fenil)-N4-(2-oxo-2,3-dihidrobenzo[d]oxazol-6-il)-5-metilpirimidin-2,4-diamina; I-106 sal trifluoroacetato de N4-(benzoxazolin-2-on-5-il)-N2-(3-trifluorometoxifenil)-5-metilpirimidin-2,4-diamina; I-107 sal trifluoroacetato de N4-(benzoxazolin-2-on-5-il)-N2-(3-trifluorometoxifenil)-5-fluoropirimidin-2,4-diamina; I-108 sal trifluoroacetato de N4-(benzoxazolin-2-on-5-il)-N2-(4-trifluorometoxifenil)-5-metilpirimidin-2,4-diamina; I-109 sal trifluoroacetato de N4-(benzoxazolin-2-on-5-il)-N2-(4-trifluorometoxifenil)-5-fluoropirimidin-2,4-diamina; I-110 N4-(benzoxazolin-2-on-5-il)-N2-[3-trifluorometil-4-(4-etilpiperazin-1-il)fenil]-5-metilpirimidin-2,4-diamina; I-111 N4-(benzoxazolin-2-on-5-il)-N2-[3-metil-4-(4-metilpiperazin-1-il)fenil]-5-metilpirimidin-2,4-di-amina; I-115 N4-(benzoxazolin-2-on-5-il)-N2-(3,4,5-trimetoxifenil)-5-fluoropirimidin-2,4-diamina; I-116 N2-(3-(difluorometoxi)-4-metoxifenil)-N4-(benzo[d]oxazol-2(3H)-on-5-il)-5-metilpirimidin-2,4-diamina; I-117 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-(4-trifluorometilsulfonil)fenil-5-metilpirimidin-2,4-diamina; I-118 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-(3-trifluorometilsulfonil)fenil-5-metilpirimidin-2,4-diamina; I-119 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-(3,4,5-trimetoxi)fenil-5-metilpirimidin-2,4-diamina; I-120 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-((4-(1,4-diazabiciclo[3.2.2]nonan-4-il)-3-metil)fenil)-5-metilpirimidin-2,4diamina; I-121 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-(4-(8-metil-8-azabiciclo[3.2.1]octan-3-ilamino)fenil)-5-metilpirimidin-2,4diamina; I-122 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-((4-(dihidro-1H-pirido[1,2-a]pirazin-2(6H,7H,8H,9H,9aH)-il)-3-metil)fenil) 5-metilpirimidin-2,4-diamina; I-123 N4-(benzo[d]oxazol-2(3H)-on-5-il)-N2-(4-(8-metil-2,8-diazabiciclo[3.2.1]octan-2-il)fenil)-5-metil-pirimidin-2,4diamina; I-124 N4-(benzo[tf]oxazoNn-2(3H)-ona-5-il)-5-metil-N2-[3-(morfoNn-4-il)-4-trifluorometoxifenil]-2,4-pirimidindiamina; I-125 N4-(benzo[d]oxazolm-2(3H)-on-5-il)-N2-[3-trifluorometil-2-(4-metilpiperazm-1-il)piridin-5-il]-5-metilpirimidin-2,4 diamina; I-126 ácido 4-[5-Metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzoico; I-127 N-(2-Dietilamino-etil)-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-128 5-{2-[4-(3-Dietilamino-pirrolidin-1-carbonil)-fenilamino]-5-metil-pirimidin-4-ilamino}-3H-benzooxazol-2-ona; I-129 5-[2-(4-Acetil-fenilamino)-5-metil-pirimidin-4-ilamino]-3H-benzooxazol-2-ona; I-130 5-[2-(3-Acetil-fenilamino)-5-metil-pirimidin-4-ilamino]-3H-benzooxazol-2-ona; I-131 2-Metil-5-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzonitrilo; I-132 N,N-Dimetil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-133 N-Metil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-134 sal formiato de N-ciclopropil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-135 4-[5-Metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-N-fenil-benzamida; I-136 4-[5-Metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-2-pirrolidin-1-il-benzamida; I-137 N-Etil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-138 sal del ácido N-Ciclobutil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida formico; I-139 N-Isopropil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-140 sal formiato de N-ciclopropil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-141 2-Cloro-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-142 sal del ácido N-ciclopropil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]benzamida trifluoroacético; I-143 N-Ciclopropil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-144 N-Ciclobutil-4-[5-metil-4-(2-oxo-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-145 4-[5-Metil-4-(2-oxo-3-propionil-2,3-dihidro-benzooxazol-5-ilamino)-pirimidin-2-ilamino]-benzamida; I-146 (5-(2-(4-carbamoilfenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo[d]oxazol-3(2H)-il)metilfosfato de di-tercbutilo; I-147 dihidrogenofosfato de (5-(2-(4-carbamoilfenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo [d]oxazol-3(2H)il)metilo; I-148 (5-(2-(4-carbamoilfenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo[d]oxazol-3(2H)-il)metilfosfato sódico; I-150 dihidrogenofosfato de (5-(2-(4-(ciclobutilcarbamoil)fenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo[d] oxazol3(2H)-il)metilo; I-151 (5-(2-(4-(ciclobutilcarbamoil)fenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo[d]oxazol-3(2H)-il)metilfosfato de metilo; I-152 (5-(2-(4-(ciclobutilcarbamoil)fenilamino)-5-metilpirimidin-4-ilamino)-2-oxobenzo[d]oxazol-3(2H)-il)metilfosfato de di-terc-butilo; I-153 5-[2-(4-Cloro-3-trifluorometil-fenilamino)-5-metil-pirimidin-4-ilamino]-3H-benzooxazol-2-ona;
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Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1904457B1 (en) * 2005-06-08 2017-09-06 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US20070203161A1 (en) * 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
SG172885A1 (en) * 2009-01-23 2011-08-29 Rigel Pharmaceuticals Inc Compositions and methods for inhibition of the jak pathway
SMT201700430T1 (it) 2009-06-25 2018-01-11 Alkermes Pharma Ireland Ltd Composti eterociclici per il trattamento di disturbi neurologici e psicologici
CA2766033C (en) * 2009-06-25 2016-09-20 Alkermes, Inc. Prodrugs of nh-acidic compounds
US8343954B2 (en) * 2010-07-28 2013-01-01 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
DK2624696T3 (en) 2010-10-06 2017-03-13 Glaxosmithkline Llc Corp Service Company BENZIMIDAZOLD DERIVATIVES AS PI3-KINASE INHIBITORS
EP2688890B1 (en) 2011-03-22 2017-08-30 Advinus Therapeutics Limited Substituted fused tricyclic compounds, compositions and medicinal applications thereof
US8901120B2 (en) 2011-04-01 2014-12-02 University Of Utah Research Foundation Substituted N-phenylpyrimidin-2-amine analogs as inhibitors of the Axl kinase
US8703767B2 (en) 2011-04-01 2014-04-22 University Of Utah Research Foundation Substituted N-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase BTK inhibitors
JP6129155B2 (ja) * 2011-04-12 2017-05-17 ライジェル ファーマシューティカルズ， インコーポレイテッド 同種移植片拒絶反応を抑制する方法
EP2554544A1 (en) * 2011-08-01 2013-02-06 Almirall, S.A. Pyridin-2(1h)-one derivatives as jak inhibitors
CA2858787C (en) 2011-12-15 2017-11-21 Alkermes Pharma Ireland Limited Prodrugs of tertiary amine compounds
US20130310340A1 (en) * 2012-05-16 2013-11-21 Rigel Pharmaceuticals, Inc. Method of treating muscular degradation
MX361499B (es) 2012-08-17 2018-12-06 Concert Pharmaceuticals Inc Baricitinib deuterado.
IN2015DN02008A (es) 2012-09-21 2015-08-14 Advinus Therapeutics Ltd
KR20150067298A (ko) 2012-10-04 2015-06-17 유니버시티 오브 유타 리서치 파운데이션 티로신 수용체 키나아제 btk 억제제로서의 치환된 n-(3-(피리미딘-4-일)페닐)아크릴아미드 유사체
EP3680238A1 (en) 2012-10-04 2020-07-15 University of Utah Research Foundation Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors
CN103788066A (zh) * 2012-10-31 2014-05-14 韩冰 一类保护移植器官的化合物及其用途
CA2899281C (en) * 2013-01-25 2022-05-31 Rigel Pharmaceuticals, Inc. Pyrimidinediamine compounds for use in treating or preventing autoimmune alopecia
CA2905993C (en) 2013-03-14 2022-12-06 Tolero Pharmaceuticals, Inc. Substituted 4-amino-pyrimidinyl-2-amino-phenyl derivatives and pharmaceutical compositions thereof for use as jak2 and alk2 inhibitors
WO2014168986A1 (en) 2013-04-08 2014-10-16 Brown Dennis M Therapeutic benefit of suboptimally administered chemical compounds
US9549988B2 (en) 2013-06-09 2017-01-24 RJS Biologics Pharmaceutical compounds targeted by MIF affinity-tethered moieties
TWI562990B (en) 2013-08-07 2016-12-21 Cadila Healthcare Ltd Novel compounds as inhibitors of janus kinase
CN105017159B (zh) * 2014-04-28 2019-05-17 四川大学 5-氟-2,4-二取代氨基嘧啶衍生物及其制备方法和用途
US10314942B2 (en) * 2014-06-30 2019-06-11 Bacterin International, Inc. Manufacture of biomaterial implants via three-dimensional printing technology
WO2016100452A2 (en) * 2014-12-17 2016-06-23 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
WO2017007658A1 (en) * 2015-07-07 2017-01-12 Rigel Pharmaceuticals, Inc. A combination for immune mediated cancer treatment
RU2020124922A (ru) 2015-11-26 2020-08-10 Новартис Аг Новые производные диаминопиридина
KR20230156174A (ko) 2016-07-12 2023-11-13 레볼루션 메디슨즈, 인크. 다른자리 입체성 shp2 억제제로서의 2,5-이치환 3-메틸 피라진 및 2,5,6-3치환 3-메틸 피라진
EP4285906A3 (en) * 2016-12-19 2024-03-13 Epizyme, Inc. Amine-substituted heterocyclic compounds as ehmt2 inhibitors and methods of use thereof
EP4230623A3 (en) 2017-01-23 2023-10-11 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
TWI820013B (zh) 2017-01-23 2023-11-01 美商銳新醫藥公司 作為別構ｓｈｐ２抑制劑之雙環化合物
US11672800B2 (en) 2017-04-21 2023-06-13 Epizyme, Inc. Combination therapies with EHMT2 inhibitors
AU2018274723B2 (en) 2017-05-26 2024-01-18 Cancer Research Technology Limited Benzimidazolone derived inhibitors of BCL6
CN111315735B (zh) 2017-09-04 2024-03-08 C4医药公司 二氢苯并咪唑酮
SG11202002941WA (en) 2017-10-12 2020-04-29 Revolution Medicines Inc Pyridine, pyrazine, and triazine compounds as allosteric shp2 inhibitors
WO2019099311A1 (en) * 2017-11-19 2019-05-23 Sunshine Lake Pharma Co., Ltd. Substituted heteroaryl compounds and methods of use
EP3724189B1 (en) 2017-12-15 2023-10-04 Revolution Medicines, Inc. Polycyclic compounds as allosteric shp2 inhibitors
JP7384812B2 (ja) 2018-03-05 2023-11-21 アルカームス ファーマ アイルランド リミテッド アリピプラゾール投与戦略
CA3096984A1 (en) 2018-04-05 2019-10-10 Sumitomo Dainippon Pharma Oncology, Inc. Axl kinase inhibitors and use of the same
MX2020011451A (es) * 2018-05-24 2020-12-07 Astrazeneca Ab Sal de fumarato de 5-((5-metil-2-((3,4,5-trimetilfenil)amino)pirim idin-4-il)amino)-benzo[d]oxazol-2(3h)-ona.
JP2021530554A (ja) 2018-07-26 2021-11-11 スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド 異常なａｃｖｒ１発現を伴う疾患を処置するための方法およびそこで使用するためのａｃｖｒ１阻害剤
WO2020092015A1 (en) 2018-11-02 2020-05-07 University Of Rochester Therapeutic mitigation of epithelial infection
CN113557235A (zh) 2019-03-06 2021-10-26 C4医药公司 用于药物治疗的杂环化合物
WO2021026451A1 (en) 2019-08-08 2021-02-11 Rigel Pharmaceuticals, Inc. Compounds and method for treating cytokine release syndrome
TW202207934A (zh) 2020-03-27 2022-03-01 瑞典商阿斯特捷利康公司 用於肺遞送的乾粉配製物及使用方法
CN113549018B (zh) * 2020-04-24 2024-02-27 中国药科大学 蛋白激酶抑制剂及其衍生物，制备方法、药物组合物和应用
AU2021280113B2 (en) * 2020-05-29 2023-12-21 Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. Pyrimidine compound as AXL inhibitor
WO2022188735A1 (en) * 2021-03-08 2022-09-15 Guangdong Newopp Biopharmaceuticals Co., Ltd. Heterocyclic compounds as hpk1 inhibitors
CN116178433A (zh) * 2021-11-26 2023-05-30 南京正大天晴制药有限公司 Axl激酶抑制剂的盐及其制备方法和用途
CN116178434A (zh) * 2021-11-26 2023-05-30 南京正大天晴制药有限公司 Axl激酶抑制剂的单对甲苯磺酸盐及其晶型

Family Cites Families (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4166452A (en) 1976-05-03 1979-09-04 Generales Constantine D J Jr Apparatus for testing human responses to stimuli
US4256108A (en) 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
US4265874A (en) 1980-04-25 1981-05-05 Alza Corporation Method of delivering drug with aid of effervescent activity generated in environment of use
US5087240A (en) 1983-08-18 1992-02-11 Drug Delivery Systems Inc. Transdermal drug patch with conductive fibers
US4921475A (en) 1983-08-18 1990-05-01 Drug Delivery Systems Inc. Transdermal drug patch with microtubes
US4738851A (en) 1985-09-27 1988-04-19 University Of Iowa Research Foundation, Inc. Controlled release ophthalmic gel formulation
US5163899A (en) 1987-03-20 1992-11-17 Drug Delivery Systems Inc. Transdermal drug delivery system
US5312325A (en) 1987-05-28 1994-05-17 Drug Delivery Systems Inc Pulsating transdermal drug delivery system
GB8804164D0 (en) 1988-02-23 1988-03-23 Tucker J M Bandage for administering physiologically active compound
US4882150A (en) 1988-06-03 1989-11-21 Kaufman Herbert E Drug delivery system
US5008110A (en) 1988-11-10 1991-04-16 The Procter & Gamble Company Storage-stable transdermal patch
US5088977A (en) 1988-12-21 1992-02-18 Drug Delivery Systems Inc. Electrical transdermal drug applicator with counteractor and method of drug delivery
EP0470154B1 (en) 1989-04-28 1996-06-05 Riker Laboratories, Inc. Dry powder inhalation device
US5521222A (en) 1989-09-28 1996-05-28 Alcon Laboratories, Inc. Topical ophthalmic pharmaceutical vehicles
DE69009946T2 (de) 1989-12-04 1994-11-03 Searle & Co System zur transdermalen Albuterol Applikation.
US5364833A (en) 1990-05-09 1994-11-15 Basf Aktiengesellschaft Cyclohexenone oxime ethers, their preparation and their use as herbicides
US5077033A (en) 1990-08-07 1991-12-31 Mediventures Inc. Ophthalmic drug delivery with thermo-irreversible gels of polxoxyalkylene polymer and ionic polysaccharide
JP2594486B2 (ja) 1991-01-15 1997-03-26 アルコン ラボラトリーズ インコーポレイテッド 局所的眼薬組成物
US5404871A (en) 1991-03-05 1995-04-11 Aradigm Delivery of aerosol medications for inspiration
US6060069A (en) 1991-05-20 2000-05-09 Dura Pharmaceuticals, Inc. Pulmonary delivery of pharmaceuticals
US5327883A (en) 1991-05-20 1994-07-12 Dura Pharmaceuticals, Inc. Apparatus for aerosolizing powdered medicine and process and using
US5492112A (en) 1991-05-20 1996-02-20 Dura Pharmaceuticals, Inc. Dry powder inhaler
US5352456A (en) 1991-10-10 1994-10-04 Cygnus Therapeutic Systems Device for administering drug transdermally which provides an initial pulse of drug
IL104068A (en) 1991-12-12 1998-10-30 Glaxo Group Ltd Pharmaceutical preparations in a spray without surfactant containing 1, 1, 1, 2 tetrafluoroethane or 1,1,2,3,3 petafluor N propane as propellant
DE69228827T2 (de) 1991-12-18 1999-10-21 Minnesota Mining And Mfg. Co., Saint Paul Mehrschichtige sperrstrukturen
US5320094A (en) 1992-01-10 1994-06-14 The Johns Hopkins University Method of administering insulin
EP0553769B1 (de) 1992-01-29 1996-01-03 FRANZ VÖLKL GmbH &amp; CO. SKI UND TENNIS SPORTARTIKELFABRIK KG Ballspielschläger, insbesondere Tennisschläger
US5277195A (en) 1992-02-03 1994-01-11 Dura Pharmaceuticals, Inc. Portable spirometer
US6582728B1 (en) 1992-07-08 2003-06-24 Inhale Therapeutic Systems, Inc. Spray drying of macromolecules to produce inhaleable dry powders
DK0665759T3 (da) 1992-10-19 1999-08-23 Dura Pharma Inc Tørpulverinhalator
US5672581A (en) 1993-01-29 1997-09-30 Aradigm Corporation Method of administration of insulin
US5364838A (en) 1993-01-29 1994-11-15 Miris Medical Corporation Method of administration of insulin
US6131567A (en) 1993-01-29 2000-10-17 Aradigm Corporation Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
JPH08509465A (ja) 1993-01-29 1996-10-08 マイリス メディカル コーポレーション ホルモンの肺内送達
US5743250A (en) 1993-01-29 1998-04-28 Aradigm Corporation Insulin delivery enhanced by coached breathing
US5558085A (en) 1993-01-29 1996-09-24 Aradigm Corporation Intrapulmonary delivery of peptide drugs
US5661130A (en) 1993-06-24 1997-08-26 The Uab Research Foundation Absorption enhancers for drug administration
TW402506B (en) 1993-06-24 2000-08-21 Astra Ab Therapeutic preparation for inhalation
US5506203C1 (en) 1993-06-24 2001-02-06 Astra Ab Systemic administration of a therapeutic preparation
MX9603936A (es) 1994-03-07 1997-05-31 Inhale Therapeutic Syst Metodos y composiciones para el suministro pulmonar de insulina.
IL114193A (en) 1994-06-20 2000-02-29 Teva Pharma Ophthalmic pharmaceutical compositions based on sodium alginate
ES2094688B1 (es) 1994-08-08 1997-08-01 Cusi Lab Manoemulsion del tipo de aceite en agua, util como vehiculo oftalmico y procedimiento para su preparacion.
US5780014A (en) 1995-04-14 1998-07-14 Inhale Therapeutic Systems Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin
US5645051A (en) 1995-04-21 1997-07-08 Dura Pharmaceuticals, Inc. Unit dose dry powder inhaler
US5622166A (en) 1995-04-24 1997-04-22 Dura Pharmaceuticals, Inc. Dry powder inhaler delivery system
US5700904A (en) 1995-06-07 1997-12-23 Eli Lilly And Company Preparation of an acylated protein powder
US5654007A (en) 1995-06-07 1997-08-05 Inhale Therapeutic Systems Methods and system for processing dispersible fine powders
GB9523675D0 (en) 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
IT1283911B1 (it) 1996-02-05 1998-05-07 Farmigea Spa Soluzioni oftalmiche viscosizzate con polisaccaridi della gomma di tamarindo
US5800807A (en) 1997-01-29 1998-09-01 Bausch & Lomb Incorporated Ophthalmic compositions including glycerin and propylene glycol
ZA989744B (en) 1997-10-31 2000-04-26 Lilly Co Eli Method for administering acylated insulin.
ATE261730T1 (de) 1997-12-31 2004-04-15 Univ Kansas Wasserlösliche medikamentenvorstufen tertiärer amine enthaltender medikamente und verfahren zu ihrer herstellung
US6261547B1 (en) 1998-04-07 2001-07-17 Alcon Manufacturing, Ltd. Gelling ophthalmic compositions containing xanthan gum
US6197934B1 (en) 1998-05-22 2001-03-06 Collagenesis, Inc. Compound delivery using rapidly dissolving collagen film
US6241969B1 (en) 1998-06-26 2001-06-05 Elan Corporation Plc Aqueous compositions containing corticosteroids for nasal and pulmonary delivery
US20020006901A1 (en) 1999-02-05 2002-01-17 Aldo T. Iacono Use of aerosolized cyclosporine for prevention and treatment of pulmonary disease
GB9914258D0 (en) 1999-06-18 1999-08-18 Celltech Therapeutics Ltd Chemical compounds
US7678364B2 (en) 1999-08-25 2010-03-16 Alkermes, Inc. Particles for inhalation having sustained release properties
AU2001226029A1 (en) 2000-01-10 2001-07-24 Dura Pharmaceuticals, Inc. Pharmaceutical formulation and method for pulmonary and oral delivery
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
AU2003265336B8 (en) 2002-07-29 2009-04-23 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
KR101201603B1 (ko) * 2003-07-30 2012-11-14 리겔 파마슈티칼스, 인크. 자가면역 질환의 치료 또는 예방에 사용하기 위한2,4-피리미딘디아민 화합물
EP1660458B1 (en) 2003-08-15 2012-01-25 Novartis AG 2, 4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
JP5208516B2 (ja) 2004-12-30 2013-06-12 エグゼリクシス， インコーポレイテッド キナーゼモジュレーターとしてのピリミジン誘導体および使用方法
CN101115761B (zh) 2005-01-19 2012-07-18 里格尔药品股份有限公司 2,4-嘧啶二胺化合物的前药及其应用
EP1904457B1 (en) 2005-06-08 2017-09-06 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US7713987B2 (en) * 2005-12-06 2010-05-11 Rigel Pharmaceuticals, Inc. Pyrimidine-2,4-diamines and their uses
EP2046759A1 (en) * 2006-07-21 2009-04-15 Novartis AG 2, 4 -di (arylaminio) -pyrimidine-5-carboxamide compounds as jak kinases inhibitors
GB0615619D0 (en) * 2006-08-05 2006-09-13 Astrazeneca Ab Chemical process for preparation of intermediates
JP5161233B2 (ja) * 2006-10-19 2013-03-13 ライジェル ファーマシューティカルズ， インコーポレイテッド 自己免疫疾患の処置のためのｊａｋキナーゼの阻害剤としての２，４−ピリミジンアミン誘導体
US7947698B2 (en) 2007-03-23 2011-05-24 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
WO2009063240A1 (en) * 2007-11-16 2009-05-22 Arrow Therapeutics Limited 2,4-diaminopyrimidine derivatives useful as inhibitors of aurora kinase
SG172885A1 (en) * 2009-01-23 2011-08-29 Rigel Pharmaceuticals Inc Compositions and methods for inhibition of the jak pathway
TW201107329A (en) * 2009-07-30 2011-03-01 Oncotherapy Science Inc Fused imidazole derivative having ttk inhibitory action
US8343954B2 (en) * 2010-07-28 2013-01-01 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway

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