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ECSP12012098A - Derivados de arilmetoxi isoindolina y composiciones que los comprenden y métodos para utilizar los mismos - Google Patents

Derivados de arilmetoxi isoindolina y composiciones que los comprenden y métodos para utilizar los mismos

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Publication number
ECSP12012098A
ECSP12012098A ECSP12012098A ECSP12012098A EC SP12012098 A ECSP12012098 A EC SP12012098A EC SP12012098 A ECSP12012098 A EC SP12012098A EC SP12012098 A ECSP12012098 A EC SP12012098A
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EC
Ecuador
Prior art keywords
disorders
lower alkyl
phenyl
optionally substituted
heterocycloalkyl
Prior art date
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English (en)
Inventor
Roger Chen
Alexander L Ruchelman
Ehab Khalil
Hon-Wah Man
George W Muller
Weihong Zhang
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Celgene Corp
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Publication date
Application filed by Celgene Corp filed Critical Celgene Corp
Publication of ECSP12012098A publication Critical patent/ECSP12012098A/es

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    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract

La invención se refiere a compuestos de fórmula: en la que: R es hidrógeno o alquilo inferior,R1 es -(CH2)n-(O)o-heterocicloalquilo o -C(O)-heterocicloalquilo, en el que el grupo heterociclolaquilo se sustituye opcionalmente con alquilo inferior, hidroxi, halógeno o con -(CH2)p-arilo, n es 0, 1 ó 2,o es 0 ó 1,p es 0, 1 ó 2,R2 es CF3, cicloalquilo, opcionalmente sustituido con alcoxi inferior o halógeno, o es indan-2-ilo, o es heterocicloalquilo, opcionalmente sustituido con heteroarilo, o es arilo o heteroarilo, en los que los anillos aromáticos se sustituyen opcionalmente con uno o dos sustituyentes, seleccionados de entre alquilo inferior, halógeno, heteroarilo, hidroxi, CF3, OCF3, OCH2CF3, OCH2-cicloalquilo, OCH2C(CH2OH)(CH2Cl)(CH3), S-alquilo inferior, alcoxi inferior, CH2-alcoxi inferior, alquinilo inferior o ciano, o con -C(O)-fenilo, -O-fenilo, -O-CH2-fenilo, fenilo o -CH2-fenilo, y en los que los anillos fenilo opcionalmente pueden sustituirse con halógeno, -C(O)-alquilo inferior, -C(O)-OH o -C(O)-O-alquilo inferior, o los anillos aromáticos se sustituyen opcionalmente con heterocicloalquilo, OCH2-oxetán-3-ilo o O-tetrahidropirán-4-ilo, opcionalmente sustituidos con alquilo inferior,X es un enlace, -NR'-, -CH2NH-, -CHR''-, -(CHR'')q-O-, -O-(CHR'')q- o -(CH2)2-, Y es un enlace o -CH2-R' es hidrógeno o alquilo inferior, R'' es hidrógeno, alquilo inferior, CF3, alcoxi inferior, q es 0, 1, 2 ó 3,o a una sal de adición de ácido farmacéuticamente aceptable de los mismos. Ahora se ha encontrado que los compuestos de fórmula I presentan una buena afinidad con los receptores asociados a rastros de aminas (TAARs), especialmente con TAAR1. Los compuestos pueden utilizarse para el tratamiento de la depresión, los trastornos de ansiedad, el trastorno bipolar, el trastorno de hiperactividad por déficit de atención (ADHD), los trastornos relacionados con el estrés, los trastornos psicóticos tales como la esquizofrenia, las enfermedades neurológicas tales como la enfermedad de Parkinson, los trastornos neurodegenerativos tales como la enfermedad de Alzheimer, la epilepsia, la migraña, la hipertensión, el abuso de sustancias, y trastornos metabólicos tales como trastornos de la alimentación, la diabetes, las complicaciones diabéticas, la obesidad, la dislipemia, los trastornos del consumo y asimilación de la energía, los trastornos y disfunción de la homeostasis de la temperatura corporal, los trastornos del sueño y del ritmo circadiano, y los trastornos cardiovasculares.
ECSP12012098 2010-02-11 2012-08-09 Derivados de arilmetoxi isoindolina y composiciones que los comprenden y métodos para utilizar los mismos ECSP12012098A (es)

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WO2010137547A1 (ja) 2009-05-25 2010-12-02 国立大学法人東京工業大学 中枢神経細胞の増殖及び分化に係る中核因子を含む医薬組成物
SI3202460T1 (sl) * 2010-02-11 2019-10-30 Celgene Corp Arilmetoksi izoindolin derivati in sestavki, ki jih obsegajo in metode za uporabo le-teh
CA2867134C (en) * 2011-03-28 2019-05-07 Sheila Dewitt 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds
CN103688176A (zh) 2011-04-29 2014-03-26 细胞基因公司 利用cereblon作为预报因子治疗癌和炎性疾病的方法
MX358517B (es) 2012-06-29 2018-08-24 Celgene Corp Métodos para determinar eficacia de fármacos usando proteínas asociadas a cereblon.
SG11201500998QA (en) * 2012-08-09 2015-04-29 Celgene Corp Methods of treating cancer using 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione
UA114521C2 (uk) 2012-08-09 2017-06-26 Селджин Корпорейшн Солі і тверді форми (s)-3-(4-((4-морфолінометил)-бензил)оксі)-1-оксоізоіндолін-2-іл)-піперидин-2,6-діону і композиції, які їх включають, і способи їхнього застосування
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