RU2004132203A - Индолилмалеимидные производные - Google Patents

Индолилмалеимидные производные Download PDF

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RU2004132203A
RU2004132203A RU2004132203/04A RU2004132203A RU2004132203A RU 2004132203 A RU2004132203 A RU 2004132203A RU 2004132203/04 A RU2004132203/04 A RU 2004132203/04A RU 2004132203 A RU2004132203 A RU 2004132203A RU 2004132203 A RU2004132203 A RU 2004132203A
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formula
methyl
compound
pharmaceutically acceptable
piperazinyl
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RU2004132203/04A
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RU2340610C2 (ru
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ЭВЕНУ Жан-Пьер (FR)
ЭВЕНУ Жан-Пьер
ФОН-МАТТ Петер (CH)
ФОН-МАТТ Петер
ВАГНЕР Юрген (CH)
ВАГНЕР Юрген
ЦЕНКЕ Герхард (DE)
ЦЕНКЕ Герхард
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Новартис АГ (CH)
Новартис Аг
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Priority claimed from GB0207729A external-priority patent/GB0207729D0/en
Priority claimed from GB0303323A external-priority patent/GB0303323D0/en
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Claims (10)

1. Соединение формулы I
Figure 00000001
в которой Ra обозначает Н, СН3, СН2-СН3 или изопропил,
Rb обозначает Н, галоген, C1-6алкокосигруппу или С1-6алкил, и либо
I. R представляет собой радикал формулы (а)
Figure 00000002
в которой R1 обозначает пиперазин-1-ил, необязательно замещенный СН3 в положении 3 или 4, либо 4,7-диаза-спиро[2,5]окт-7-ил,
R2 обозначает Cl, Br, CF3 или CH3, и
R3 обозначает Н, СН3 или CF3; R2 отлично от СН3 или Cl, когда R3 обозначает Н,
Ra обозначает Н или СН3, Rb обозначает Н, и R1 обозначает 4-метил-1-пиперазинил, либо
II. R обозначает радикал формулы (б)
Figure 00000003
в которой R4 обозначает 1-пиперазинил, замещенный СН3 в положениях 3 и/или 4, или 4,7-диаза-спиро[2,5]окт-7-ил; Ra отлично от Н или СН3, когда R4 обозначает 4-метил-1-пиперазинил; либо
III. R обозначает остаток формулы (в)
Figure 00000004
в которой R14 обозначает 1-пиперазинил, необязательно замещенный СН3 в положении 3 и/или 4 или в положении 3 этилом, фенил-С1-4-алкилом, С1-4алкокси-С1-4алкилом или галоген-С1-4алкилом; или 4,7-диаза-спиро[2.5]окт-7-ил,
R15 обозначает галоген, CF3 или СН3, R15 отлично от СН3, когда R16 обозначает СН3, Ra обозначает Н или СН3, Rb обозначает Н, и R14 обозначает 4-метил-1-пиперазинил, и
R16 обозначает Н, СН3, СН2-СН3 или CF3, R16 отлично от Н, когда R15 обозначает Cl, Ra обозначает Н или СН3, Rb обозначает Н, и R14 обозначает 4-метил-1-пиперазинил, либо
IV. R представляет собой радикал формулы (г)
Figure 00000005
в которой R8 обозначает 1-пиперазинил, 3-метил-пиперазин-1-ил или 4-бензил-пиперазин-1-ил, либо
V. R представляет собой радикал формулы (д)
Figure 00000006
в которой R9 обозначает 4,7-диаза-спиро[2,5]окт-7-ил или пиперазин-1-ил, замещенный в положении 3 метилом или этилом и необязательно метилом в положении 4, или его соль.
2. Соединение по п.1, которое выбрано из 3-[5-хлор-6-метил-2-(4-метил-пиперазин-1-ил)-пиримидин-4-ил]-4-(1Н-индол-3-ил)-пиррол-2,5-диона, 3-[3-(4,7-диаза-спиро[2,5]окт-7-ил)-изохинолин-1-ил]-4-(7-метил-1Н-индол-3-ил)-пиррол-2,5-диона и 3-(1Н-индол-3-ил)-4-[2-(4-метил-пиперазин-1-ил)-5-трифторметил-пиримидин-4-ил]пиррол-2,5-диона, или их солей.
3. Способ получения соединения формулы I по п.1, который включает взаимодействие соединения формулы II
Figure 00000007
в котором Ra и Rb такие, как определено в п.1, с соединением формулы III
Figure 00000008
в котором R такое, как определено в п.1,
и, в случае необходимости, превращение конечного соединения формулы I, полученного в свободной форме, в солевую форму или наоборот.
4. Соединение формулы I по п.1 или 2 в свободной форме или в форме фармацевтически приемлемой соли для применения в качестве фармацевтического препарата.
5. Фармацевтическая композиция, включающая соединение формулы I по п.1 или 2 или его фармацевтически приемлемую соль в сочетании с его фармацевтически приемлемым разбавителем или носителем.
6. Соединение формулы I по п.1 или 2 или его фармацевтически приемлемая соль, предназначенное для получения фармацевтической композиции для лечения или профилактики нарушений или заболеваний, опосредованных Т-лимфоцитами и/или ПКС либо GSK-3β.
7. Соединение формулы I по п.1 или 2 или его фармацевтически приемлемая соль, предназначенное для применения в комбинации с иммунодепрессантом, иммуномодулирующим, противовоспалительным, антипролиферативным или антидиабетическим лекарственным препаратом.
8. Комбинация, включающая а) соединение формулы I в свободной форме или в форме фармацевтически приемлемой соли и б) по меньшей мере один второй агент, выбранный из иммунодепрессанта, иммуномодулирующего, противовоспалительного, антипролиферативного или антидиабетического лекарственного препарата.
9. Способ профилактики или лечения нарушений или заболеваний, опосредованных Т-лимфоцитами и/или ПКС либо GSK-3β у субъекта, нуждающегося в таком лечении, включающий введение субъекту эффективного количества соединения формулы I по п.1 или 2 или его фармацевтически приемлемой соли.
10. Способ по п.9, включающий совместное введение одновременно или последовательно терапевтически эффективного количества соединения формулы I в свободной форме или в форме фармацевтически приемлемой соли и второй лекарственной субстанции, которая представляет собой иммунодепрессант, иммуномодулирующий, противовоспалительный, антипролиферативный или антидиабетический лекарственный препарат.
RU2004132203/04A 2002-04-03 2003-04-02 Индолилмалеимидные производные, способ их получения, их применение и фармацевтическая композиция для лечения или профилактики нарушений или заболеваний, опосредованных т-лимфоцитами и/или пкс RU2340610C2 (ru)

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GB0207729A GB0207729D0 (en) 2002-04-03 2002-04-03 Organic compounds
GB0207729.5 2002-04-03
GB0303323.0 2003-02-13
GB0303323A GB0303323D0 (en) 2003-02-13 2003-02-13 Organic compounds

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US (5) US20050119274A1 (ru)
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