RU2016122731A - Функционализированные и замещенные индолы в качестве противораковых агентов - Google Patents

Функционализированные и замещенные индолы в качестве противораковых агентов Download PDF

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RU2016122731A
RU2016122731A RU2016122731A RU2016122731A RU2016122731A RU 2016122731 A RU2016122731 A RU 2016122731A RU 2016122731 A RU2016122731 A RU 2016122731A RU 2016122731 A RU2016122731 A RU 2016122731A RU 2016122731 A RU2016122731 A RU 2016122731A
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Айан ДЖЕЙМС
Айан ДИКСОН
Джон Фьютрилл
Энтони КАЗЗАП
Херберт ТРОЙТЛАЙН
Цзюнь ЦЗЭН
Трейси НЕРО
Питер ГАННИНГ
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Claims (98)

1. Соединение формулы (I)
Figure 00000001
или его фармацевтически приемлемое лекарственное средство или пролекарство, где:
R1 представляет собой
Figure 00000002
Figure 00000003
R2 представляет собой N(R6)2, CH(R6)2, индол,
Figure 00000004
Figure 00000005
R3 представляет собой Н, NH2, N(R6)2, OR4,
Figure 00000006
X1 представляет собой (СН2)0-5;
Х2 и Х3 представляют собой О, NH, NHR5', SO2, С(О), C(O)NH, (СН2)0-5, С(O)(СН2)1-5, NH(CH2)1-5, CHR5', CHC(R5')C(O), пиразол, изооксазол;
Х4 представляет собой О, NH, NR6;
R4, R5 и R6 представляют собой Н, СН3, СН2СН3;
R6 представляет собой Н, СН3, (СН2)1-5СН3, (CH2)1-5OCH3, CF3, CN, OCF3;
R7 представляет собой Н, ОН, алкил, галоген, алкокси, гидроксиалкил, амино, аминоалкил, диаминоалкил или диоксолановое кольцо, конденсированное с 2 смежными атомами углерода R1 или R2.
2. Соединение по п. 1, где X1 представляет собой СН2, (СН2)2 или (СН2)3.
3. Соединение по п. 1, где R3 представляет собой N(R6)2.
4. Соединение по п. 3, где R6 представляет собой СН3.
5. Соединение по п. 1, где R3 представляет собой Н.
6. Соединение по п. 1, где R3 представляет собой
Figure 00000007
7. Соединение по п. 1, где R3 представляет собой
Figure 00000008
8. Соединение по п. 7, где Х4 представляет собой NR5.
9. Соединение по п. 8, где R5 представляет собой СН3.
10. Соединение по п. 1, где R4 представляет собой СН3 или Н.
11. Соединение по п. 1, где R5 представляет собой СН3 или Н.
12. Соединение по п. 1, где Х2 представляет собой СН2, О, (СН2)0, NH или С(О).
13. Соединение по п. 1, где R1 представляет собой
Figure 00000009
14. Соединение по п. 1, где R1 представляет собой
Figure 00000010
15. Соединение по п. 13 или 14, где R7 представляет собой Н.
16. Соединение по любому из пп. 1-12, где R1 представляет собой
Figure 00000011
17. Соединение по п. 1, где Х3 представляет собой (СН2)2, C(O)NH, СН2, (СН2)0, О или CHR5'.
18. Соединение по п. 17, где R5' представляет собой СН3.
19. Соединение по п. 1, где R2 представляет собой
Figure 00000012
a R7 представляет собой Н, ОН, галоген, алкокси или диоксолановое кольцо.
20. Соединение по п. 19, где галоген представляет собой F.
21. Соединение по п. 19, где алкокси представляет собой ОСН3.
22. Соединение по п. 1, где R2 представляет собой
Figure 00000013
23. Соединение по п. 22, где Х4 представляет собой О.
24. Соединение по п. 22, где Х4 представляет собой NR6.
25. Соединение по п. 24, где R6 представляет собой СН3.
26. Соединение по п. 1, где R2 представляет собой
Figure 00000014
a R7 представляет собой Н.
27. Соединение по п. 1, где R2 представляет собой CH(R6)2.
28. Соединение по п. 27, где R6 представляет собой СН3.
29. Соединение по п. 1, где R2 представляет собой N(R6)2.
30. Соединение по п. 29, где R6 представляет собой СН3.
31. Соединение по п. 1, где R2 представляет собой
Figure 00000015
a R7 представляет собой гидроксиалкил.
32. Соединение по п. 31, где гидроксиалкил представляет собой СН2ОН.
33. Соединение по п. 1, где соединение выбрано из группы, состоящей из:
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
34. Фармацевтическая композиция для лечения или профилактики пролиферативного заболевания, где композиция включает соединение по любому из пп. 1-33.
35. Способ лечения или профилактики пролиферативного заболевания, включающий введение субъекту терапевтически эффективного количества соединения по любому из пп. 1-33.
36. Применение соединения по любому из пп. 1-33 для лечения или профилактики пролиферативного заболевания.
37. Применение соединения по любому из пп. 1-33 или фармацевтической композиции по п. 34 в производстве лекарственного средства для лечения или профилактики пролиферативного заболевания.
38. Фармацевтическая композиция по п. 34, способ по п. 35 или применение по п. 36 или 37, где пролиферативное заболевание представляет собой рак.
39. Фармацевтическая композиция для профилактики рецидива солидной опухоли, где композиция включает соединение по любому из пп. 1-33.
40. Способ профилактики рецидива солидной опухоли, включающий введение терапевтически эффективного количества соединения по любому из пп. 1-33.
41. Применение соединения по любому из пп. 1-33 для профилактики рецидива солидной опухоли.
42. Применение соединения по любому из пп. 1-33 или фармацевтической композиции по п. 39 в производстве лекарственного средства для профилактики рецидива солидной опухоли.
RU2016122731A 2013-11-25 2014-11-25 Функционализированные и замещенные индолы в качестве противораковых агентов RU2016122731A (ru)

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PCT/AU2014/050372 WO2015074123A1 (en) 2013-11-25 2014-11-25 Functionalised and substituted indoles as anti-cancer agents

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CN110229091B (zh) * 2019-06-21 2022-11-22 天津科技大学 具有白三烯a4水解酶抑制作用的1，5-二取代吲哚衍生物及应用
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WO2015074123A1 (en) 2015-05-28
MX2016006707A (es) 2016-11-29
PH12016500967A1 (en) 2016-06-20
CN105916841A (zh) 2016-08-31
KR20160089409A (ko) 2016-07-27
IL245673A0 (en) 2016-06-30
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US20170166555A1 (en) 2017-06-15
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