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RU2007101685A - Модуляторы никотиновых ацетилхолиновых рецепторов альфа 7 и их терапевтические применения - Google Patents

Модуляторы никотиновых ацетилхолиновых рецепторов альфа 7 и их терапевтические применения Download PDF

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RU2007101685A
RU2007101685A RU2007101685/04A RU2007101685A RU2007101685A RU 2007101685 A RU2007101685 A RU 2007101685A RU 2007101685/04 A RU2007101685/04 A RU 2007101685/04A RU 2007101685 A RU2007101685 A RU 2007101685A RU 2007101685 A RU2007101685 A RU 2007101685A
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RU2007101685/04A
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RU2403247C2 (ru
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Джованни ГАВИРАГИ (IT)
Джованни ГАВИРАГИ
Кь ра ГИРОН (IT)
Кьяра Гирон
Хендрик БОТМАНН (IT)
Хендрик Ботманн
Ренца РОНКАРАТИ (IT)
Ренца РОНКАРАТИ
Георг Кристиан ТЕРСТАППЕНН (IT)
Георг Кристиан ТЕРСТАППЕНН
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СЬЕНА БИОТЕК С.п.А. (IT)
СЬЕНА БИОТЕК С.п.А.
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    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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Claims (8)

1. Соединение общей формулы (I):
Figure 00000001
где Y представляет собой группу -CONH(Q)- или -NHCONH(Q)-;
Q представляет собой 5-10-членное ароматическое или гетероароматическое кольцо;
R представляет собой водород; галоген; линейный, разветвленный или циклический (С1-С6)алкил, галогеноалкил, алкокси или ацил; гидрокси; циано; нитро; моно- или ди-(С1-С6)алкиламино, ациламино или алкиламинокарбонил; карбамоил; (С6-С10)арил- или (С1-С6)алкилсульфониламино; (С6-С10)арил- или (С1-С6)алкилсульфамоил; 5-10-членное ароматическое или гетероароматическое кольцо, возможно замещенное: галогеном; линейным, разветвленным или циклическим (С1-С3)алкилом, галогеноалкилом, алкокси или ацилом; гидрокси; циано; нитро; амино; моно- или ди-(С1-С6)алкиламино, ациламино или алкиламинокарбонильной группами; карбамоилом; (С6-С10)арил- или (С1-С6)алкилсульфониламино; (С6-С10)арил- или (С1-С6)алкилсульфамоилом;
Х представляет собой группу
Figure 00000002
;
где Z представляет собой СН2, N или О;
m представляет собой целое число от 1 до 4;
р равен 0, 1 или 2;
R'', независимо друг от друга для р равного 2, выбран из группы, состоящей из водорода; моно- или ди-[линейного, разветвленного или циклического (С1-С6)алкил]аминокарбонила; линейного, разветвленного или циклического (С1-С6)алкила, алкокси, ацила;
его соли, изомеры, диастереомеры или рацемические смеси,
за исключением следующих соединений:
N-[4-(диметиламино)фенил]-1-пиперидинпентанамида,
N-(4-ацетилфенил)-1-пиперидинпентанамида,
N-(4-метоксифенил)-1-пиперидинпентанамида,
N-(4-нитрофенил)-1-пиперидинпентанамида,
N-фенил-1-пиперидинпентанамида,
N-(4-метилфенил)-1-пиперидинпентанамида,
N-(4-хлорфенил)-1-пиперидинпентанамида.
2. Соединение по п.1, где Y представляет собой -CONH(Q)-;
Q представляет собой 5-10-членное ароматическое или гетероароматическое кольцо;
R выбран из группы, состоящей из фенила; нафтила; пиридила; пиримидинила; хинолинила; изохинолинила; индолила; тиенила; бензотиенила; фуранила; бензофуранила; имидазолила; бензоимидазолила; пирролила; возможно замещенных, как указано в п.1;
Х представляет собой группу
Figure 00000002
;
где Z представляет собой CH2, N или О;
m представляет собой целое число от 1 до 4;
р равен 0, 1 или 2;
R'', независимо друг от друга, когда р равен 2, выбран из группы, состоящей из водорода; моно- или ди-[линейного, разветвленного или циклического (С1-С6)алкил]аминокарбонила; линейного, разветвленного или циклического (С1-С6)алкила, алкокси, ацила.
3. Соединение по п.1, где Y представляет собой -NHCONH(Q)-;
Q представляет собой 5-10-членное ароматическое или гетероароматическое кольцо;
R выбран из группы, состоящей из галогена; линейного, разветвленного или циклического (С1-С6)алкила, алкокси или алкиламино; галогеноалкила; фенила; нафтила; пиридила; пиримидинила; хинолинила; изохинолинила; индолила; тиенила; бензотиенила; фуранила; бензофуранила; имидазолила; бензоимидазолила; пирролила; возможно замещенных, как указано в п.1;
Х представляет собой группу
Figure 00000002
;
Z представляет собой CH2, N или О;
m представляет собой целое число от 1 до 4;
р равен 0, 1 или 2;
R'', независимо друг от друга, когда р равен 2, выбран из группы, состоящей из водорода; моно- или ди-[линейного, разветвленного или циклического (С1-С6)алкил]аминокарбонила; линейного, разветвленного или циклического (С1-С6)алкила, алкокси, ацила.
4. Фармацевтическая композиция, содержащая соединение по любому из пп.1-3 в комбинации с фармацевтически приемлемым носителем или эксципиентом.
5. Применение соединения по любому из пп.1-3 для получения лекарства для лечения неврологических, психиатрических, когнитивных, иммунологических и воспалительных расстройств.
6. Применение по п.5 для лечения болезни Альцгеймера.
7. Способ предупреждения или лечения заболеваний, состояний или дисфункций, связанных с никотиновыми ацетилхолиновыми рецепторами (nAChR) альфа 7, включающий введение субъекту, нуждающемуся в этом, эффективного количества соединения по любому из пп.1-3.
8. Способ по п.7 для предупреждения или лечения нейродегенеративного заболевания, в частности болезни Альцгеймера и шизофрении.
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