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RU2018111712A - Соединение, имеющее действие ингибирования агрегации тромбоцитов, и его соль, и содержащая такие соединения композиция для предупреждения или лечения тромботических заболеваний - Google Patents

Соединение, имеющее действие ингибирования агрегации тромбоцитов, и его соль, и содержащая такие соединения композиция для предупреждения или лечения тромботических заболеваний Download PDF

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RU2018111712A
RU2018111712A RU2018111712A RU2018111712A RU2018111712A RU 2018111712 A RU2018111712 A RU 2018111712A RU 2018111712 A RU2018111712 A RU 2018111712A RU 2018111712 A RU2018111712 A RU 2018111712A RU 2018111712 A RU2018111712 A RU 2018111712A
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hydroxy
methanone
dihydroxyphenyl
aryl
pyridin
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RU2018111712A
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RU2739915C2 (ru
RU2018111712A3 (ru
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Дзей Ман РИУ
Донг Вон ЛИ
Канг Хиеок ЛИ
Дзин Хун ПАРК
Геум Сил ЧО
Ки Сунг ЛИ
Дзин Хо ЧУНГ
Воо Иле ПАРК
Дзае Йоунг ЛИ
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Син Поонг Фармасьютикал Ко., Лтд.
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Claims (43)

1. СОЕДИНЕНИЕ, ПРЕДСТАВЛЕННОЕ ПРИВЕДЕННЫМИ ДАЛЕЕ ФОРМУЛАМИ (I) ИЛИ (II), ИЛИ ЕГО ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМАЯ СОЛЬ ИЛИ ИЗОМЕР,
[ФОРМУЛА I]
Figure 00000001
[Формула II]
Figure 00000002
в которых
R1 представляет собой гидрокси или C1-C10-алкокси;
X представляет собой N или O;
R2 представляет собой -(CH2)p-(5-12-членный гетероцикл)-(CH2)p-C6-C12-арил, 5-12-членный гетероцикл, -(CH2)p-NHC(=O)-C6-C12-арил, -CHR4R5, 5-12-членный гетероарил, C6-C12-арил, -C6-C12-арил-O-(5-12-членный гетероарил), -(CH2)p-(5-12-членный гетероарил) или -(CH2)p-C6-C12-арил,
причем p равен целому числу от 1 до 10; R4 и R5 представляют собой, каждый независимо, C1-C6-алкоксикарбонил или -CH2-(5-12-членный гетероарил); указанные гетероцикл и гетероарил могут содержать от 1 до 3 гетероатомов, выбранных из N, O и S; и указанные гетероцикл, гетероарил и арил могут быть замещены 1-4 заместителями, выбранными из группы, включающей галоген, оксо, аминокарбонил, C1-C6-алкил, нитро, C1-C6-алкокси, нитрил, C1-C6-алкиламинокарбонил, гидрокси и гидрокси-C1-C6-алкил;
R3 представляет собой водород;
когда X представляет собой O, R3 не существует;
когда X представляет собой N, X, взятый вместе с R2 и R3, может образовывать 5-12-членный гетероцикл, содержащий 1-3 гетероатома, выбранных из O, N и S; причем указанный гетероцикл может быть замещен C6-C12-арилом; 6-12-членный гетероарил, содержащий 1-3 гетероатома, выбранных из O, N и S, который является незамещенным или замещен галогеном; или -O-CHR6R7; и причем R6 и R7 представляют собой, каждый независимо, C6-C12-арил или 6-10-членный гетероарил, содержащий 1-3 гетероатома, выбранных из O, N и S, которые оба являются незамещенными или замещены галогеном.
2. Соединение по п.1, причем соединение выбирают из группы, включающей
(6,7-дигидротиено[3,2-c]пиридин-5(4H)-ил)(3,4-дигидроксифенил)метанон;
(3,4-дигидроксифенил)(4-(5-фторбензо[d]изоксазол-3-ил)пиперидин-1-ил)метанон;
N-((4-(4-фторбензил)морфолин-2-ил)метил)-3,4-дигидроксибензамид;
3,4-дигидрокси-N-(2-оксотетрагидротиофен-3-ил)бензамид;
N,N'-(нонан-1,9-диил)бис(3,4-дигидроксибензамид);
(4-((4-хлорфенил)(пиридин-2-ил)метокси)пиперидин-1-ил)(3,4-дигидроксифенил)метанон;
(S)-(4-((4-хлорфенил)(пиридин-2-ил)метокси)пиперидин-1-ил)(3,4-дигидроксифенил)метанон;
(S)-метил-2-(3,4-дигидроксибензамидо)-3-(1H-индол-3-ил)пропаноат;
4-(3,4-дигидроксибензамидо)-1-метил-3-пропил-1H-пиразол-5-карбоксамид;
2-метил-4-оксо-4H-пиран-3-ил-3,4-дигидроксибензоат;
(3,4-дигидроксифенил)(4-фенилпиперазин-1-ил)метанон;
(6,7-дигидротиено[3,2-c]пиридин-5(4H)-ил)(4-гидрокси-3-метоксифенил)метанон;
2-этил-4-оксо-4H-пиран-3-ил-4-гидрокси-3-метоксибензоат;
2-метил-4-оксо-4H-пиран-3-ил-4-гидрокси-3-метоксибензоат;
4-гидрокси-3-метокси-N-(4-метокси-2-нитрофенил)бензамид;
N-(3-этилфенил)-4-гидрокси-3-метоксибензамид;
4-(4-(4-гидрокси-3-метоксибензамидо)фенокси)-N-метилпиколинамид;
4-((4-хлорфенил)(пиридин-2-ил)метокси)пиперидин-1-ил)(4-гидрокси-3-метоксифенил)метанон;
4-гидрокси-N-((3-гидрокси-5-(гидроксиметил)-2-метилпиридин-4-ил)метил)-3-метоксибензамид;
(6,7-дигидротиено[3,2-c]пиридин-5(4H)-ил)(2,5-дигидроксифенил)метанон;
(4-((4-хлорфенил)(пиридин-2-ил)метокси)пиперидин-1-ил)(2,5-дигидроксифенил)метанон;
N-((4-(4-фторбензил)морфолин-2-ил)метил)-2,5-дигидроксибензамид;
(2,5-дигидроксифенил)(4-(5-фторбензо[d]изоксазол-3-ил)пиперидин-1-ил)метанон;
N-(3,4-диметоксифенетил)-2,5-дигидроксибензамид;
2,5-дигидрокси-N-(2-(тиофен-2-ил)этил)бензамид и
2,5-дигидрокси-N-(2-оксотетрагидротиофен-3-ил)бензамид,
или его фармацевтически приемлемая соль или изомер.
3. Композиция для предупреждения или лечения тромботических заболеваний, включающая в качестве активного ингредиента соединение по п. 1 или 2 или его фармацевтически приемлемую соль или изомер.
4. Композиция по п.3, причем тромботические заболевания выбирают из группы, включающей эмболию легких, тромбофлебит, портальный тромбоз, стенокардию, артериосклероз и церебральный инфаркт.
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