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RU2018128334A - Ингибиторы индоламин-2,3-диоксигеназы (ido) - Google Patents

Ингибиторы индоламин-2,3-диоксигеназы (ido) Download PDF

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RU2018128334A
RU2018128334A RU2018128334A RU2018128334A RU2018128334A RU 2018128334 A RU2018128334 A RU 2018128334A RU 2018128334 A RU2018128334 A RU 2018128334A RU 2018128334 A RU2018128334 A RU 2018128334A RU 2018128334 A RU2018128334 A RU 2018128334A
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RU2018128334A
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Син ДАЙ
Яолинь Ван
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Инвентисбио Инк.
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Claims (47)

1. Соединение формулы (I)
Figure 00000001
или его фармацевтически приемлемая соль,
где W представляет собой -О-, -S- или связь;
Q представляет собой -C(=O)NH- или связь;
Y представляет собой -CR8= или -N=, в соответствии с допустимой валентностью;
R1 представляет собой -С(=O)ОН, -C(=O)OR10, замещенный или незамещенный гетероциклил, замещенный или незамещенный гетероарил, -NHSO2R9, -C(=O)NHSO2R9, -C(=O)NHC(=O)OR10 или -SO2NHC(=O)R10;
R2 и R3 каждый независимо представляет собой водород, галоген, замещенный или незамещенный C1-C6 алкил, замещенный или незамещенный C1-С6 алкокси, или R2 и R3 связаны с образованием замещенного или незамещенного 3-8-членного карбоциклического кольца или замещенного или незамещенного 3-8-членного гетероциклического кольца;
R4 и R5 каждый независимо представляет собой водород, замещенный или незамещенный C1-С6 алкил, замещенный или незамещенный С2-С6 алкенил, замещенный или незамещенный C5-C8 циклоалкенил, замещенный или незамещенный С2-С10 алкинил, замещенный или незамещенный C1-С6 алкокси, замещенный или незамещенный С3-C8 циклоалкил, замещенный или незамещенный 3-12-членный гетероциклил, замещенный или незамещенный 5-6-членный моноциклический гетероарил, замещенный или незамещенный 8-10-членный бициклический гетероарил, замещенный или незамещенный арил или арилсульфонил; или R4 и R5 связаны с атомом N, к которому они присоединены, с образованием необязательно замещенного моноциклического или бициклического гетероциклила;
R6 представляет собой замещенный или незамещенный C1-С6 алкил, замещенный или незамещенный С3-С8 циклоалкил, замещенный или незамещенный С2-С6 алкенил, замещенный или незамещенный С2-С6 алкинил, замещенный или незамещенный C5-C8 циклоалкенил, замещенный или незамещенный арил, замещенный или незамещенный 4-7-членный моноциклический гетероциклил, замещенный или незамещенный 7-10-членный бициклический гетероциклил, замещенный или незамещенный 5-6-членный моноциклический гетероарил, замещенный или незамещенный 8-10-членный бициклический гетероарил, замещенный или незамещенный C1-С6 алкокси, замещенный или незамещенный арилокси или -C(=O)R7;
R7 представляет собой водород, замещенный или незамещенный C1-С6 алкил или замещенный или незамещенный арил;
R8 представляет собой водород, галоген, -CN, -ОН, замещенный или незамещенный C1-С6 алкил или замещенный или незамещенный C1-C6 алкокси; и
R9 и R10 каждый независимо представляет собой водород, замещенный или незамещенный C1-С6 алкил, или замещенный или незамещенный С2-С6алкенил.
2. Соединение по п. 1, отличающееся тем, что указанное соединение имеет формулу (II)
Figure 00000002
или его фармацевтически приемлемая соль.
3. Соединение по любому из пп. 1-2, отличающееся тем, что R1 представляет собой С(=O)ОН или
Figure 00000003
4. Соединение по любому из пп. 1-3, отличающееся тем, что R2 и R3 связаны с образованием замещенного или незамещенного 3-6-членного карбоциклического кольца или замещенного или незамещенного 3-8-членного гетероциклического кольца.
5. Соединение по любому из пп. 1-4, отличающееся тем, что R2 и R3 связаны с образованием замещенного или незамещенного циклопропильного, замещенного или незамещенного циклобутильного, замещенного или незамещенного циклопентильного, или замещенного или незамещенного циклогексильного кольца.
6. Соединение по любому из пп. 1-5, отличающееся тем, что R4 и R5 каждый независимо представляет собой замещенный или незамещенный C1-С6 алкил, замещенный или незамещенный С3-С8 циклоалкил, или замещенный или незамещенный 3-12-членный гетероциклил.
7. Соединение по п. 6, отличающееся тем, что R4 и R5, каждый независимо, имеют формулу
Figure 00000004
Figure 00000005
где R представляет собой замещенный или незамещенный C1-С6 алкил.
8. Соединение по любому из пп. 1-7, отличающееся тем, что R6 имеет формулу:
Figure 00000006
где R6A представляет собой водород, замещенный или незамещенный C1-С6 алкил, галоген, -CN, -OR6a или замещенную или незамещенную сульфонильную группу;
где R6a представляет собой водород или замещенный или незамещенный C1-С6 алкил; и
k равен 0, 1 или 2.
9. Соединение по любому из пп. 1-8, отличающееся тем, что R6 имеет формулу
Figure 00000007
10. Соединение по п. 1, отличающееся тем, что указанное соединение представляет собой
Figure 00000008
Figure 00000009
Figure 00000010
или его фармацевтически приемлемая соль.
11. Соединение по п. 1, отличающееся тем, что указанное соединение представляет собой
Figure 00000011
Figure 00000012
или его фармацевтически приемлемая соль.
12. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-11 или его фармацевтически приемлемую соль и фармацевтически приемлемое вспомогательное вещество.
13. Способ лечения заболевания, связанного с IDO, включающий введение субъекту, нуждающемуся в этом, эффективного количества соединения по любому из пп. 1-11 или его фармацевтически приемлемой соли, или фармацевтической композиции, содержащей эффективное количество соединения по любому из пп. 1-11 или его фармацевтически приемлемой соли.
14. Способ по п. 13, отличающийся тем, что указанное заболевание, связанное с IDO, представляет собой рак.
15. Способ по п. 13, отличающийся тем, что указанное заболевание, связанное с IDO, представляет собой рак, выбранный из группы, состоящей из рака легких, рака молочной железы, рака предстательной железы, рака яичников, эндометриального рака, рака шейки матки, рака мочевого пузыря, рака головы и шеи, почечено-клеточной карциномы, рака пищевода, рака поджелудочной железы, рака головного мозга, раковых заболеваний желудочно-кишечного тракта, рака печени, лейкоза, лимфомы, меланомы, множественной миеломы, саркомы Юинга и остеосаркомы.
16. Способ по любому из пп. 13-15, дополнительно включающий лечение субъекта дополнительной противораковой терапией.
17. Способ по п. 16, отличающийся тем, что указанная дополнительная противораковая терапия представляет собой иммунотерапию, лучевую терапию, химиотерапию, клеточную терапию или хирургию.
18. Способ по п. 16, отличающийся тем, что указанная дополнительная противораковая терапия включает противораковый агент.
19. Способ по п. 13, отличающийся тем, что указанное заболевание, связанное с IDO, представляет собой инфекционное заболевание.
20. Способ по п. 19, отличающийся тем, что указанное инфекционное заболевание представляет собой вирусную инфекцию, и указанного субъекта дополнительно лечат дополнительной противовирусной терапией.
21. Способ по п. 20, отличающийся тем, что указанная дополнительная противовирусная терапия включает дополнительный противовирусный агент или противовирусную вакцину.
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