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RU2013157877A - Модуляторы атф-связывающих кассетных транспортеров - Google Patents

Модуляторы атф-связывающих кассетных транспортеров Download PDF

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RU2013157877A
RU2013157877A RU2013157877/04A RU2013157877A RU2013157877A RU 2013157877 A RU2013157877 A RU 2013157877A RU 2013157877/04 A RU2013157877/04 A RU 2013157877/04A RU 2013157877 A RU2013157877 A RU 2013157877A RU 2013157877 A RU2013157877 A RU 2013157877A
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Сара Хадида С. РУА
Петер Д. Й. Гротенхейс
Гур Фредрик Ван
Марк Т. МИЛЛЕР
Джейсон МАККАРТНИ
Цзинлань ЧЖОУ
Брайан БЕАР
Мехди Мишель Джамель Нума
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Вертекс Фармасьютикалз Инкорпорейтед
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Abstract

1. Соединение, выбранное из2. Соединение3. Соединение4. Соединение5. Фармацевтическая композиция, содержащая(i) соединение по п. 1 и(ii) фармацевтически приемлемый носитель.6. Композиция по п. 5, дополнительно содержащая дополнительное средство, выбранное из муколитического средства, бронхолитического средства, антибиотика, антибактериального средства, противовоспалительного средства, корректора CFTR, усилителя CFTR или питательного средства.7. Композиция по п. 5 или 6, в которой соединение представляет собой8. Композиция по п. 5 или 6, в которой соединение представляет собой9. Композиция по п. 5 или 6, в которой соединение представляет собой10. Способ повышения количества функцинальных ABC-транспортеров в мембране клетки, включающий стадию контактирования указанной клетки с соединением, выбранным из11. Способ по п. 10, в котором ABC-транспортер представляет собой CFTR.12. Способ по п. 10 или 11, в котором соединение представляет собой13. Способ по п. 10 или 11, в котором соединение представляет собой14. Способ по п. 10 или 11, в котором соединение представляет собой15. Способ лечения состояния, заболевания или расстройства у пациента, в патологии которого задействована активность ABC-транспортера, включающий стадию введения указанному пациенту соединения, выбранного из16. Способ по п. 15, в котором указанное состояние, заболевание или расстройство выбрано из муковисцидоза, наследственной эмфиземы, наследственного гемохроматоза,недостаточностей факторов свертывания крови и фибринстабилизирующего фактора, таких как дефицит белка С, наследственный ангионеврологический отек 1 типа, дефектов в процессинге липидов, таких как семейная гиперхолестер

Claims (25)

1. Соединение, выбранное из
Figure 00000001
Figure 00000002
2. Соединение
Figure 00000003
3. Соединение
Figure 00000004
4. Соединение
Figure 00000005
5. Фармацевтическая композиция, содержащая
(i) соединение по п. 1 и
(ii) фармацевтически приемлемый носитель.
6. Композиция по п. 5, дополнительно содержащая дополнительное средство, выбранное из муколитического средства, бронхолитического средства, антибиотика, антибактериального средства, противовоспалительного средства, корректора CFTR, усилителя CFTR или питательного средства.
7. Композиция по п. 5 или 6, в которой соединение представляет собой
Figure 00000006
8. Композиция по п. 5 или 6, в которой соединение представляет собой
Figure 00000007
9. Композиция по п. 5 или 6, в которой соединение представляет собой
Figure 00000008
10. Способ повышения количества функцинальных ABC-транспортеров в мембране клетки, включающий стадию контактирования указанной клетки с соединением, выбранным из
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
11. Способ по п. 10, в котором ABC-транспортер представляет собой CFTR.
12. Способ по п. 10 или 11, в котором соединение представляет собой
Figure 00000013
13. Способ по п. 10 или 11, в котором соединение представляет собой
Figure 00000014
14. Способ по п. 10 или 11, в котором соединение представляет собой
Figure 00000015
15. Способ лечения состояния, заболевания или расстройства у пациента, в патологии которого задействована активность ABC-транспортера, включающий стадию введения указанному пациенту соединения, выбранного из
Figure 00000016
Figure 00000017
Figure 00000018
16. Способ по п. 15, в котором указанное состояние, заболевание или расстройство выбрано из муковисцидоза, наследственной эмфиземы, наследственного гемохроматоза,
недостаточностей факторов свертывания крови и фибринстабилизирующего фактора, таких как дефицит белка С, наследственный ангионеврологический отек 1 типа, дефектов в процессинге липидов, таких как семейная гиперхолестеринемия, хиломикронемия 1 типа, абеталипопротеинемия, лизосомных болезней, таких как болезнь клеточных включений/псевдо-Хюрлера, мукополисахаридозы, болезнь Сандхоффа/Тея-Сакса, болезнь Криглера-Найяра II типа, полиэндокринопатия/гиперинсулинемия, сахарный диабет, карликовость Ларона, дефицит милеопероксидазы, первичный гипопаратиреоидизм, меланома, гликогеноз CDG 1 типа, наследственная эмфизема, врожденный гипертиреоидизм, несовершенный остеогенез, наследственная гипофибриногенемия, недостаточность ACT, несахарный диабет (di), нейрофизиологический di, нефрогенный DI, синдром Шарко-Мари-Тута, болезнь Пелицеуса-Мерцбахера, нейродегенеративных заболеваний, таких как болезнь Альцгеймера, болезнь Паркинсона, боковой амиотрофический склероз, прогрессирующий супрануклеарный паралич, болезнь Пика, некоторых неврологических расстройств, связанных с обменом глутамина, таких как болезнь Гентингтона, спинномозговая атаксия I типа, спинально-бульбарная мышечная атрофия, дентаторубральная и паллидолюисовая атрофия и миотоническая дистрофия, а также губчатых энцефалопатий, таких как наследственная болезнь Крейтцфельдта-Якоба, болезнь Фабри, синдром Штраусслера-Шейнкера, хроническое обструктивное заболевание легких (COPD), болезнь сухих глаз и синдром Шегрена.
17. Способ по п. 15 или 16, в котором соединение представляет собой
Figure 00000019
18. Способ по п. 15 или 16, в котором соединение представляет собой
Figure 00000020
19. Способ по п. 15 или 16, в котором соединение представляет собой
Figure 00000021
20. Набор для измерения активности ABC-транспортера или его фрагмента в биологическом образце in vitro или in vivo, содержащий
(i) первую композицию, содержащую соединение, выбранное из соединения по п. 1; и
(ii) инструкции для
а) контактирования композиции с биологическим образцом;
b) измерения активности указанного ABC-транспортера или его
фрагмента.
21. Набор по п. 20, дополнительно содержащий инструкции для
а) контактирования дополнительной композиции с биологическим образцом;
b) измерения активности указанного ABC-транспортера или его фрагмента в присутствии указанного дополнительного соединения и
c) сравнения активности ABC-транспортера в присутствии дополнительного соединения с плотностью ABC-транспортера в присутствии указанной первой композиции.
22. Набор по п. 20, предназначенный для измерения плотности CFTR.
23. Набор по любому из пп. 20-22, в котором соединение представляет собой
Figure 00000022
24. Набор по любому из пп. 20-22, в котором соединение представляет собой
Figure 00000023
25. Набор по любому из пп. 20-22, в котором соединение представляет собой
Figure 00000024
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