RU2345993C2 - ЛАКТАМСОДЕРЖАЩЕЕ СОЕДИНЕНИЕ И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Xa - Google Patents

ЛАКТАМСОДЕРЖАЩЕЕ СОЕДИНЕНИЕ И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Xa Download PDF

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RU2345993C2
RU2345993C2 RU2004112191/04A RU2004112191A RU2345993C2 RU 2345993 C2 RU2345993 C2 RU 2345993C2 RU 2004112191/04 A RU2004112191/04 A RU 2004112191/04A RU 2004112191 A RU2004112191 A RU 2004112191A RU 2345993 C2 RU2345993 C2 RU 2345993C2
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Russia
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thromboembolic
disease
thromboembolic disease
pharmaceutical composition
agent
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RU2004112191/04A
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RU2004112191A (ru
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Доналд Пинто (US)
Доналд Пинто
Мими КВАН (US)
Мими КВАН
Майкл ОРУЭТ (US)
Майкл ОРУЭТ
Юн-Лонг ЛИ (US)
Юн-Лонг ЛИ
Вей ХАН (US)
Вей Хан
Дженнифер КИАО (US)
Дженнифер КИАО
Патрик ЛЭМ (US)
Патрик ЛЭМ
Стефани КОЧ (US)
Стефани КОЧ
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Бристол-Маерс Сквибб Компани
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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Abstract

Описывается новое лактамсодержащее соединение - производное тетрагидро-1Н-пиразоло[3,4-с]пиридин-3-карбоксамида формулы I
Figure 00000179
его фармацевтически приемлемая соль и фармацевтические композиции, их содержащие, и их применение в качестве ингибитора фактора Ха. Данное соединение может быть использовано для лечения тромбоэмболических заболеваний. 9 н. и 33 з.п. ф-лы, 9 табл.

Description

Текст описания приведен в факсимильном виде.
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Claims (42)

1. Соединение формулы 1:
Figure 00000177
,
или его фармацевтически приемлемая соль.
2. Соединение по п.1, представляющее собой соединение формулы 1
Figure 00000178
,
3. Соединение по п.1 или 2, предназначенное для лечения тромбоэмболического заболевания.
4. Соединение по п.1 или 2, предназначенное для изготовления медикамента для лечения тромбоэмболического заболевания.
5. Соединение по п.3 или 4, отличающееся тем, что тромбоэмболическое заболевание представляет собой заболевание из группы, состоящей из артериальных сердечно-сосудистых тромбоэмболических заболеваний, венозных сердечно-сосудистых тромбоэмболических заболеваний и тромбоэмболических заболеваний в камере сердца.
6. Соединение по п.3 или 4, отличающееся тем, что тромбоэмболическое заболевание представляет собой острый коронарный синдром.
7. Соединение по п.3 или 4, отличающееся тем, что тромбоэмболическое заболевание представляет собой инфаркт миокарда, переходное ишемическое нарушение или инсульт.
8. Соединение по п.3 или 4, отличающееся тем, что тромбоэмболическое заболевание представляет собой глубокий тромбоз вены.
9. Соединение по п.3 или 4, отличающееся тем, что тромбоэмболическое заболевание представляет собой легочную эмболию.
10. Фармацевтическая композиция для лечения тромбоэмболического заболевания, содержащая фармацевтически приемлемый носитель и терапевтически эффективное количество соединения формулы (1) по п.1 или его фармацевтически приемлемой соли.
11. Фармацевтическая композиция для лечения тромбоэмболического заболевания, содержащая фармацевтически приемлемый носитель и терапевтически эффективное количество соединения по п.2.
12. Фармацевтическая композиция по п.10 или 11, отличающаяся тем, что тромбоэмболическое заболевание представляет собой заболевание, выбранное из группы, состоящей из артериальных сердечно-сосудистых тромбоэмболических заболеваний, венозных сердечно-сосудистых тромбоэмболических заболеваний и тромбоэмболических заболеваний в камере сердца.
13. Фармацевтическая композиция по п.10 или 11, отличающаяся тем, что тромбоэмболическое заболевание представляет собой острый коронарный синдром.
14. Фармацевтическая композиция по п.10 или 11, отличающаяся тем, что тромбоэмболическое заболевание представляет собой инфаркт миокарда, переходное ишемическое нарушение или инсульт.
15. Фармацевтическая композиция по п.10 или 11, отличающаяся тем, что тромбоэмболическое заболевание представляет собой глубокий тромбоз вены.
16. Фармацевтическая композиция по п.10 или 11, отличающаяся тем, что тромбоэмболическое заболевание представляет собой легочную эмболию.
17. Применение соединения по п.1 или 2 для изготовления медикамента для лечения тромбоэмболического заболевания.
18. Применение соединения по п.1 или 2 для лечения тромбоэмболического заболевания.
19. Применение по п.17 или 18, при котором тромбоэмболическое заболевание представляет собой заболевание из группы, состоящей из артериальных сердечно-сосудистых тромбоэмболических заболеваний, венозных сердечно-сосудистых тромбоэмболических заболеваний и тромбоэмболических заболеваний в камере сердца.
20. Применение по п.17 или 18, при котором тромбоэмболическое заболевание представляет собой острый коронарный синдром.
21. Применение по п.17 или 18, при котором тромбоэмболическое заболевание представляет собой инфаркт миокарда, переходное ишемическое нарушение или инсульт.
22. Применение по п.17 или 18, при котором тромбоэмболическое заболевание представляет собой глубокий тромбоз вены.
23. Применение по п.17 или 18, при котором тромбоэмболическое заболевание представляет собой легочную эмболию.
24. Применение фармацевтической композиции по п.10 или 11 для изготовления медикамента для лечения тромбоэмболического заболевания.
25. Применение фармацевтической композиции по п.10 или 11 для лечения тромбоэмболического заболевания.
26. Применение по п.24 или 25, при котором тромбоэмболическое заболевание представляет собой заболевание из группы, состоящей из артериальных сердечно-сосудистых тромбоэмболических заболеваний, венозных сердечно-сосудистых тромбоэмболических заболеваний и тромбоэмболических заболеваний в камере сердца.
27. Применение по п.24 или 25, при котором тромбоэмболическое заболевание представляет собой острый коронарный синдром.
28. Применение по п.24 или 25, при котором тромбоэмболическое заболевание представляет собой инфаркт миокарда, переходное ишемическое нарушение или инсульт.
29. Применение по п.24 или 25, при котором тромбоэмболическое заболевание представляет собой глубокий тромбоз вены.
30. Применение по п.24 или 25, при котором тромбоэмболическое заболевание представляет собой легочную эмболию.
31. Фармацевтическая композиция для лечения тромбоэмболического заболевания, содержащая соединение по п.2, и второй терапевтический агент, представляющий собой по меньшей мере один агент, выбранный из ингибитора фактора Ха, противокоагулянтного агента, противотромбоцитного агента, тромбинингибирующего агента, тромболитического агента и фибринолитического агента.
32. Фармацевтическая композиция по п.31, отличающаяся тем, что второй терапевтический агент выбирают из варфарина, нефракционированного гепарина, низкомолекулярного гепарина, синтетического пентасахарида, ирудина, аргатробанаса, аспирина, ибупрофена, напроксена, сулиндака, индометацина, мефенамата, дроксикама, диклофинака, сульфинпиразона, пироксикама, тиклопидина, клопидогреля, тирофибана, эптифибатида, абсиксимаба, мелагатрана, дисульфатоксирудина, тканевого плазминогенного активатора, модифицированного плазминогенного активатора ткани, анистреплазы, урокиназы и стрептокиназы.
33. Фармацевтическая композиция по п.31, отличающаяся тем, что второй терапевтический агент представляет собой по меньшей мере один противотромбоцитный агент.
34. Фармацевтическая композиция по п.31, отличающаяся тем, что второй терапевтический агент выбран из аспирина и клопидогреля.
35. Фармацевтическая композиция по п.34, отличающаяся тем, что противотромбоцитный агент представляет собой клопидогрель.
36. Фармацевтическая композиция по п.34, отличающаяся тем, что противотромбоцитный агент представляет собой аспирин.
37. Применение фармацевтической композиции по п.31 для изготовления средства для лечения тромбоэмболического заболевания.
38. Применение по п.37, отличающееся тем, что второй терапевтический агент выбирают из варфарина, нефракционированного гепарина, низкомолекулярного гепарина, синтетического пентасахарида, ирудина, аргатробанаса, аспирина, ибупрофена, напроксена, сулиндака, индометацина, мефенамата, дроксикама, диклофинака, сульфинпиразона, пироксикама, тиклопидина, клопидогреля, тирофибана, эптифибатида, абсиксимаба, мелагатрана, дисульфатоксирудина, тканевого плазминогенного активатора, модифицированного плазминогенного активатора ткани, анистреплазы, урокиназы и стрептокиназы.
39. Применение по п.37, отличающееся тем, что второй терапевтический агент представляет собой по меньшей мере один противотромбоцитный агент.
40. Применение по п.37, отличающееся тем, что второй терапевтический агент выбран из аспирина и клопидогреля.
41. Применение по п.37, отличающееся тем, что противотромбоцитный агент представляет собой клопидогрель.
42. Применение по п.37, отличающееся тем, что противотромбоцитный агент представляет собой аспирин.
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