RU2004103625A - Новые производные мандальной кислоты и их применение в качестве ингибиторов тромбина - Google Patents

Новые производные мандальной кислоты и их применение в качестве ингибиторов тромбина Download PDF

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RU2004103625A
RU2004103625A RU2004103625/04A RU2004103625A RU2004103625A RU 2004103625 A RU2004103625 A RU 2004103625A RU 2004103625/04 A RU2004103625/04 A RU 2004103625/04A RU 2004103625 A RU2004103625 A RU 2004103625A RU 2004103625 A RU2004103625 A RU 2004103625A
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compound
pharmaceutically acceptable
acceptable derivative
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RU2341516C2 (ru
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Тор ИНГХАРДТ (SE)
Тор ИНГХАРДТ
Андерс ЙОХАНССОН (SE)
Андерс Йоханссон
Арне СВЕНССОН (SE)
Арне СВЕНССОН
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Астразенека Аб (Se)
Астразенека Аб
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Claims (28)

1. Соединение формулы I
Figure 00000001
или его фармацевтически приемлемое производное.
2. Фармацевтически приемлемое производное соединения формулы I как оно определено в п.1, причем это производное соединение представляет собой соединение формулы Ia
Figure 00000002
где R1 представляет собой OR2 или C(O)OR3;
R2 представляет собой Н, С1-10алкил, С1-3алкиларил или C1-3алкилоксиарил (алкильные части двух последних групп возможно прерваны одним или более чем одним атомом кислорода, а арильные части двух последних групп возможно замещены одним или более чем одним заместителем, выбранным из галогено, фенила, метила или метокси, причем последние три группы также возможно замещены одним или более чем одним заместителем, представляющим собой галогено); и
R3 представляет собой С1-10алкил (эта последняя группа возможно прервана одним или более чем одним атомом кислорода) или С1-3алкиларил, или С1-3алкилоксиарил (алкильные части двух последних групп возможно прерваны одним или более чем одним атомом кислорода, а арильные части двух последних групп возможно замещены одним или более чем одним заместителем, выбранным из галогено, фенила, метила или метокси, причем последние три группы также возможно замещены одним или более чем одним заместителем, представляющим собой галогено), или его фармацевтически приемлемое производное.
3. Соединение по п.2, где R1 представляет собой OR2.
4. Соединение по п.3, где R2 представляет собой Н или незамещенный, линейный, разветвленный или циклический C1-8алкил.
5. Соединение по п.4, где R2 представляет собой Н или С1-6алкил.
6. Соединение по п.4, где R2 представляет собой линейный С1-3алкил, разветвленный С3-8алкил или циклический С4-7алкил.
7. Соединение по п.5, где R2 представляет собой метил, этил, н-пропил, изо-пропил или циклобутил.
8. Соединение по п.7, где R2 представляет собой метил.
9. Соединение по п.1 или 2, где фрагмент
Figure 00000003
находится в S-конфигурации.
10. Соединение по п.1 или 2, где фрагмент
Figure 00000004
находится в R-конфигурации.
11. Соединение по п.1, которое представляет собой Ph(3-Cl)(5-OCHF2)-(R)CH(OH)C(O)-(S)Aze-Pab(2,6-diF).
12. Соединение по п.2, которое представляет собой:
Ph(3-Cl)(5-OCHF2)-(R)CH(OH)C(0)-(S)Aze-Pab(2,6-diF)(OMe) или
Ph(3-Cl)(5-OCHF2)-(R)CH(OH)C(O)-(S)Aze-Pab(2,6-diF)(OH).
13. Фармацевтический препарат, включающий в себя соединение, как оно определено в любом из пп.1-12, или его фармацевтически приемлемое производное в смеси с фармацевтически приемлемым адъювантом, разбавителем или носителем.
14. Соединение по п.1 или 2 или его фармацевтически приемлемое производное для применения в качестве фармацевтического средства.
15. Соединение по п.1 или 2 или его фармацевтически приемлемое производное для применения в лечении состояния, при котором требуется ингибирование тромбина.
16. Соединение по п.1 или 2 или его фармацевтически приемлемое производное для применения в лечении состояния, при котором показана антикоагулянтная терапия.
17. Соединение по п.1 или 2 или его фармацевтически приемлемое производное для применения в лечении тромбоза.
18. Соединение по п.1 или 2 или его фармацевтически приемлемое производное для применения в качестве антикоагулянта.
19. Применение соединения, как оно определено в любом из пп.1-12, или его фармацевтически приемлемого производного в качестве активного ингредиента для изготовления лекарства для лечения состояния, при котором требуется ингибирование тромбина.
20. Применение соединения, как оно определено в любом из пп.1-12, или его фармацевтически приемлемого производного в качестве активного ингредиента для изготовления лекарства для лечения состояния, при котором показана антикоагулянтная терапия.
21. Применение по п.19 или 20, где состояние представляет собой тромбоз.
22. Применение по п.19 или 20, где состояние представляет собой гиперкоагуляцию в крови и/или тканях.
23. Применение соединения, как оно определено в любом из пп.1-12, или его фармацевтически приемлемого производного в качестве активного ингредиента для изготовления антикоагулянта.
24. Способ лечения состояния, при котором требуется ингибирование тромбина, при котором лицу, страдающему таким состоянием или подверженному такому состоянию, вводят терапевтически эффективное количество соединения, как оно определено в любом из пп.1-12, или его фармацевтически приемлемого производного.
25. Способ лечения состояния, при котором показана антикоагулянтная терапия, при котором лицу, страдающему таким состоянием или подверженному такому состоянию, вводят терапевтически эффективное количество соединения, как оно определено в любом из пп.1-12, или его фармацевтически приемлемого производного.
26. Способ по п.24 или 25, при котором такое состояние представляет собой тромбоз.
27. Способ по п.24 или 25, при котором такое состояние представляет собой гиперкоагуляцию в крови и/или тканях.
28. Способ получения соединения формулы I, как оно определено в п.1, при котором:
(1) осуществляют сочетание соединения формулы II
Figure 00000005
с соединением формулы III
Figure 00000006
(2) осуществляют сочетание соединения формулы IV
Figure 00000007
с соединением формулы V
RU2004103625/04A 2001-08-30 2002-08-30 Новые производные миндальной кислоты и их применение в качестве ингибиторов тромбина RU2341516C2 (ru)

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