RU2016124136A - Дикетоны и гидроксикетоны в качестве активатора сигнального пути катенина - Google Patents
Дикетоны и гидроксикетоны в качестве активатора сигнального пути катенина Download PDFInfo
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Claims (45)
1. Соединение или его фармацевтически приемлемая соль или пролекарство, имеющее структуру формулы I:
где R1 выбирают из группы, состоящей из замещенного или незамещенного гетероарила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу;
R2 выбирают из группы, состоящей из замещенного или незамещенного арила, замещенного или незамещенного гетероарила, замещенного или незамещенного карбоциклила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу; и
R3, R4, R5 и R6 независимо выбирают из группы, состоящей из H, -C1-9алкила, -C1-9алкиларила и -C1-9алкилгетероарила.
2. Соединение по п.1, где R1 выбирают из группы, состоящей из
4. Соединение по п.1, где R3, R4, R5 и R6 представляют собой H.
5. Соединение по п.1, имеющее структуру, выбранную из группы, состоящей из:
6. Соединение или его фармацевтически приемлемая соль или пролекарство, имеющее структуру формулы II:
где R1 выбирают из группы, состоящей из замещенного или незамещенного гетероарила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу;
R2 выбирают из группы, состоящей из замещенного или незамещенного арила, замещенного или незамещенного гетероарила, замещенного или незамещенного карбоциклила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу; и
R3 и R4 независимо выбирают из группы, состоящей из H, -C1-9алкила, -C1-9алкиларила и -C1-9алкилгетероарила.
7. Соединение по п.6, где R1 выбирают из группы, состоящей из
9. Соединение по п.6, где R3 и R4 представляют собой H.
10. Соединение по п.6, имеющее структуру, выбранную из группы, состоящей из:
11. Соединение или его фармацевтически приемлемая соль или пролекарство, имеющее структуру формулы III
где R1 выбирают из группы, состоящей из замещенного или незамещенного арила, замещенного или незамещенного гетероарила, замещенного или незамещенного карбоциклила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу;
R2 выбирают из группы, состоящей из замещенного или незамещенного арила, замещенного или незамещенного гетероарила, замещенного или незамещенного карбоциклила и замещенного или незамещенного гетероциклила, при условии, что углеродный атом присоединен к карбонилу; и
R3 и R4 независимо выбирают из группы, состоящей из H, -C1-9алкила, -C1-9алкиларила и -C1-9алкилгетероарила.
12. Соединение по п.11, имеющее структуру, выбранную из группы, состоящей из:
13. Фармацевтическая композиция, включающая терапевтически эффективное количество соединения по любому одному из пп.1, 6 или 11, или его фармацевтически приемлемой соли, и фармацевтически приемлемое вспомогательное вещество.
14. Фармацевтическая композиция по п.13, где композиция может применяться в качестве вводимого лекарственного средства в покрытие, высвобождающее лекарственное средство, для медицинского устройства.
15. Способ активации передачи сигнала Wnt с целью лечения расстройства или заболевания у пациента, где способ включает введение пациенту терапевтически эффективного количества соединения по любому одному из пп.1, 6 или 11, или его фармацевтически приемлемой соли.
16. Способ по п.15, где расстройство или заболевание представляет собой нейродегенеративное заболевание.
17. Способ по п.16, где нейродегенеративное заболевание представляет собой болезнь Паркинсона, удары, ишемическое церебральное заболевание, эпилепсию, болезнь Альцгеймера, депрессивное состояние, биполярное расстройство или шизофрению.
18. Способ по п.15, где расстройство или заболевание представляет собой глазное заболевание.
19. Способ по п.18, где глазное заболевание представляет собой возрастную макулярную дегенерацию, диабетический макулярный отек, наследственную эксудативную витреоретинопатию или пигментный ретинит.
20. Способ по п.15, где расстройство или заболевание относится к дифференцировке и росту стволовых клеток, такое как выпадение волос, заболевания, относящиеся к гемопоэзу, заболевания, относящиеся к регенерации тканей, и другие заболевания, связанные с нарушениями развития, дифференцировки стволовых клеток и пролиферации клеток.
21. Способ по п.15, где расстройство или заболевание представляет собой остеопороз, остеоартропатию, несовершенный остеогенез, дефекты костей, переломы костей, пародонтоз, отосклероз, заживление раны, черепно-лицевые дефекты и онколитическое заболевание костей.
22. Способ по п.15, где пациентом является человек.
23. Способ по п.15, где соединение активирует один или более белков в сигнальном пути Wnt.
24. Способ по п.23, где соединение активирует передачу сигнала, индуцируемую одним или более Wnt белками.
25. Способ по п.24, где Wnt белки выбирают из: WNT1, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11 и WNT16.
26. Покрытие, высвобождающее лекарственное средство, включающее соединение по пп.1, 6, или 11, или его фармацевтически приемлемую соль.
27. Медицинское устройство, включающее соединение по пп.1, 6, или 11, или его фармацевтически приемлемую соль.
28. Имплантат, губка, полимер, или гелеобразная композиция, применяемые для in vivo использования, включающие соединение по пп.1, 6, или 11, или его фармацевтически приемлемую соль.
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