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RU2308454C2 - Соединения, композиции на их основе и способы их использования - Google Patents

Соединения, композиции на их основе и способы их использования Download PDF

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RU2308454C2
RU2308454C2 RU2004133325/04A RU2004133325A RU2308454C2 RU 2308454 C2 RU2308454 C2 RU 2308454C2 RU 2004133325/04 A RU2004133325/04 A RU 2004133325/04A RU 2004133325 A RU2004133325 A RU 2004133325A RU 2308454 C2 RU2308454 C2 RU 2308454C2
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Эндрю МАКДОНАЛЬД (US)
Эндрю Макдональд
Густав БЕРДЖИНС (US)
Густав Берджинс
Байниан ФЕНГ (US)
Байниан ФЕНГ
Дэвид Джей Си. Младший МОРГАНС (US)
Дэвид Джей Си. Младший МОРГАНС
Стивен Дэвид НАЙТ (US)
Стивен Дэвид Найт
Кеннет А. НЬЮЛЭНДЕР (US)
Кеннет А. НЬЮЛЭНДЕР
Дашь нт ДХЭНЭК (US)
Дашьянт ДХЭНЭК
Кристофер С. БРУК (US)
Кристофер С. Брук
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Цитокинетикс, Инк.
Смитклайн Бихем Корпорейшн
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Abstract

Изобретение относится к новым бензопиран-4-онам, имеющим структуру
Figure 00000001
где:
R1 - радикал, выбранный из группы, включающей бензил, хлорбензил, метилбензил, метоксибензил, цианобензил, гидроксибензил и диметоксибензил;
R2 и R2' - один из радикалов, каждый из которых независимо выбран из группы, включающей водород, C1-C4 алкил, и замещенный C1-C4 алкил;
R12 является -N(R4)(COR3);
R3 - радикал, выбранный из группы, включающей фенил и фенил, замещенный C1-C4 алкилом;
R4 - радикал, выбранный из группы, включающей C1-C4 алкил и C1-C4 алкил, замещенный аминогруппой;
R5, R6 и R8 являются водородом;
R7 - радикал, выбранный из группы, включающей водород, галоген, гидроксил, C1-C4 алкокси и циано, в том числе отдельные стереоизомеры и смеси стереоизомеров. Изобретение также относится к фармацевтической композиции на основе этих соединений, способу модуляции активности кинезина KSP, способу ингибирования митотического кинеза KSP и способам использования этих соединений для приготовления лекарственных средств для лечения клеточно-пролиферативных заболеваний. 6 н. и 13 з.п. ф-лы, 3 ил., 4 табл.

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Текст описания приведен в факсимильном виде
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Claims (19)

1. Лекарственное соединение, имеющее структуру:
Figure 00000140
где R1 - радикал, выбранный из группы, включающей бензил, хлорбензил, метилбензил, метоксибензил, цианобензил, гидроксибензил и диметоксибензил;
R2 и R2' - один из радикалов, каждый из которых независимо выбран из группы, включающей: водород, C1-C4 алкил, и замещенный C1-C4 алкил;
R12 - является -N(R4)(COR3);
R3 - радикал, выбранный из группы, включающей фенил и фенил, замещенный C1-C4 алкилом;
R4 - радикал, выбранный из группы, включающей C1-C4 алкил и C1-C4 алкил, замещенный аминогруппой;
R5, R6, и R8 - являются водородом;
R7 - радикал, выбранный из группы, включающей водород, галоген, гидроксил, C1-C4 алкокси и циано, в том числе отдельные стереоизомеры и смеси стереоизомеров.
2. Соединение по п.1, отличающееся тем, что оно является основой фармацевтически приемлемой соли.
3. Соединение по п.1, отличающееся тем, что оно является основой фармацевтически приемлемого сольвата.
4. Соединение по п.1, отличающееся тем, что оно является основой фармацевтически приемлемого сольвата фармацевтически приемлемой соли соединения по п.1.
5. Соединение по п.2, отличающееся тем, что оно является солью хлористоводородной кислоты.
6. Соединение по п.1, отличающееся тем, что R1 является бензилом.
7. Соединение по п.1, отличающееся тем, что R2 является этилом или пропилом, a R2' является водородом.
8. Соединение по п.1, отличающееся тем, что R2 является i-пропилом.
9. Соединение по п.1, отличающееся тем, что каждый из R2 и R2' присоединены к стереогенному центру, имеющему R-конфигурацию, или к фармацевтически приемлемой соли этого соединения или ее сольвату.
10. Соединение по п.1, отличающееся тем, что R4 является аминоэтилом, аминопропилом, аминобутилом, метиламиноэтилом, метиламинопропилом, метиламинобутилом, диметиламиноэтилом, диметиламинопропилом, диметиламинобутилом, этиламиноэтилом, этиламинопропилом, этиламинобутилом.
11. Соединение по п.1, отличающееся тем, что R4 является аминопропилом.
12. Соединение по п.1, отличающееся тем, что R7 является циано, метокси или галогеном.
13. Соединение по п.12, отличающееся тем, что R7 является хлорогруппой.
14. Соединение по п.1, отличающееся тем, что R1 является бензилом; R2 является водородом, этилом или пропилом; R2' является водородом; R5 является водородом; R6 является водородом; R7 является циано, метокси или галогеном, или водородом; R8 является водородом; R12 - является -N(R4)(COR3), при этом R4, является аминопропилом;
15. Лекарственная композиция для ингибирования митотического кинеза KSP, содержащая фармацевтический наполнитель и соединение по п.1, или соль этого соединения, или ее сольват.
16. Способ модуляции активности кинезина KSP, включающий в себя обеспечение контакта указанного кинезина с эффективным количеством соединения по п.1 или фармацевтически приемлемой солью этого соединения или ее сольватом.
17. Способ ингибирования митотического кинезина KSP, включающий в себя обеспечение контакта указанного кинезина с эффективным количеством соединения по п.1 или фармацевтически приемлемой солью этого соединения или ее сольватом.
18. Способ использования соединения по п.1 или фармацевтически приемлемой соли этого соединения или ее сольвата по средствам изготовления лекарственного средства для лечения клеточно-пролиферативного заболевания.
19. Способ использования соединения по п.1 посредством изготовления лекарственного средства для лечения нарушения, связанного с активностью кинезина KSP.
RU2004133325/04A 2002-04-17 2003-04-11 Соединения, композиции на их основе и способы их использования RU2308454C9 (ru)

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