RU2010128512A - Гетероциклические ингибиторы мек и способы их применения - Google Patents

Гетероциклические ингибиторы мек и способы их применения Download PDF

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RU2010128512A
RU2010128512A RU2010128512/04A RU2010128512A RU2010128512A RU 2010128512 A RU2010128512 A RU 2010128512A RU 2010128512/04 A RU2010128512/04 A RU 2010128512/04A RU 2010128512 A RU2010128512 A RU 2010128512A RU 2010128512 A RU2010128512 A RU 2010128512A
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Russia
Prior art keywords
fluoro
phenylamino
methylthio
carboxamide
oxo
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RU2010128512/04A
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English (en)
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Эллисон Л. МАРЛОУ (US)
Эллисон Л. МАРЛОУ
Эли УОЛЛЭС (US)
Эли УОЛЛЭС
Джеонгбеоб СЕО (US)
Джеонгбеоб СЕО
Джозеф П. ЛИССИКАТОС (US)
Джозеф П. ЛИССИКАТОС
Хонг Вун ЯНГ (US)
Хонг Вун ЯНГ
Джим БЛЕЙК (US)
Джим БЛЕЙК
Ричард Энтони СТОРИ (SE)
Ричард Энтони СТОРИ
Ребекка Джейн БУТ (SE)
Ребекка Джейн БУТ
Джон Дэвид ПИТТАМ (SE)
Джон Дэвид ПИТТАМ
Джон ЛЕОНАРД (SE)
Джон ЛЕОНАРД
Марк Ричард ФИЛДИНГ (SE)
Марк Ричард ФИЛДИНГ
Original Assignee
Астразенека Аб (Se)
Астразенека Аб
Эррэй Биофарма Инк. (Us)
Эррэй Биофарма Инк.
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Application filed by Астразенека Аб (Se), Астразенека Аб, Эррэй Биофарма Инк. (Us), Эррэй Биофарма Инк. filed Critical Астразенека Аб (Se)
Publication of RU2010128512A publication Critical patent/RU2010128512A/ru

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    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

1. Соединение, имеющее формулу V: ! ! или его фармацевтически приемлемая соль, где: ! R3 представляет собой HOCH2CH2O или (S)-МеСН(ОН)CH2O; и ! R9 представляет собой Н, СН3, F или Cl, ! при условии, что когда R9 представляет собой Cl, тогда R3 не может представлять собой НОСН2СН2О. ! 2. Соединение по п.1, выбранное из: ! 2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида; ! (S)-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида; ! 2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1,5-диметил-6-оксо-1,6-дигидропиридин-3-карбоксамида; ! (S)-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1,5-диметил-6-оксо-1,6-дигидропиридин-3-карбоксамида; ! 5-фтор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида; ! (S)-5-фтор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида; и ! (S)-5-хлор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида. ! 3. Соединение по любому из пп.1 или 2 для применения в качестве лекарственного средства, которое ингибирует МЕК (киназа митогенактивируемых ERK (киназ, регулируемых внеклеточными сигналами)). ! 4. Соединение по любому из пп.1 или 2 для применения в качестве лекарственного средства для лечения гиперпролиферативного расстройства или воспалительного состояния. ! 5. Применение соединения по любому из пп.1 или 2 в изготовлении лекарственного средства для лечения гиперпролиферативного расстройства или воспалительного состояния. ! 6. Фармацевтическая композиция, которая ингибирует МЕК, содержащая соединение по любому

Claims (6)

1. Соединение, имеющее формулу V:
Figure 00000001
или его фармацевтически приемлемая соль, где:
R3 представляет собой HOCH2CH2O или (S)-МеСН(ОН)CH2O; и
R9 представляет собой Н, СН3, F или Cl,
при условии, что когда R9 представляет собой Cl, тогда R3 не может представлять собой НОСН2СН2О.
2. Соединение по п.1, выбранное из:
2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида;
(S)-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида;
2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1,5-диметил-6-оксо-1,6-дигидропиридин-3-карбоксамида;
(S)-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1,5-диметил-6-оксо-1,6-дигидропиридин-3-карбоксамида;
5-фтор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксиэтокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида;
(S)-5-фтор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида; и
(S)-5-хлор-2-(2-фтор-4-(метилтио)фениламино)-N-(2-гидроксипропокси)-1-метил-6-оксо-1,6-дигидропиридин-3-карбоксамида.
3. Соединение по любому из пп.1 или 2 для применения в качестве лекарственного средства, которое ингибирует МЕК (киназа митогенактивируемых ERK (киназ, регулируемых внеклеточными сигналами)).
4. Соединение по любому из пп.1 или 2 для применения в качестве лекарственного средства для лечения гиперпролиферативного расстройства или воспалительного состояния.
5. Применение соединения по любому из пп.1 или 2 в изготовлении лекарственного средства для лечения гиперпролиферативного расстройства или воспалительного состояния.
6. Фармацевтическая композиция, которая ингибирует МЕК, содержащая соединение по любому из пп.1 или 2 вместе с фармацевтически приемлемым носителем.
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