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RU2472791C2 - Соединения, модулирующие внутриклеточный кальций - Google Patents

Соединения, модулирующие внутриклеточный кальций Download PDF

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RU2472791C2
RU2472791C2 RU2011108969/04A RU2011108969A RU2472791C2 RU 2472791 C2 RU2472791 C2 RU 2472791C2 RU 2011108969/04 A RU2011108969/04 A RU 2011108969/04A RU 2011108969 A RU2011108969 A RU 2011108969A RU 2472791 C2 RU2472791 C2 RU 2472791C2
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compound according
disease
alkyl
phenyl
compound
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RU2011108969A (ru
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Гонул ВЕЛИСЕЛЕБИ
Кеннет А. СТОДЕРМАН
Джеффри П. УИТТЕН
Яжонг ПЕЙ
Цзяньгуо ЦАО
Чжицзунь ВАНГ
Эван РОДЖЕРС
Брайан Дик
Джонатан ГРЕЙ
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КалсиМедика Инк.
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Abstract

Изобретение относится к соединениям формулы (I):
Figure 00000466
где: A, J, R1, R4, X, Z представлены в п.1 формулы изобретения, а также к фармацевтической композиции, содержащей такие соединения, модулирующие активность депо-управляемых кальциевых (SOC) каналов. Кроме того, в данном изобретении описаны способы применения таких модуляторов SOC-каналов для лечения заболеваний или состояний, при которых может быть полезно ингибирование активности SOC-каналов. 4 н. и 13 з.п. ф-лы, 5 табл., 2 ил., 8 пр.

Description

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Figure 00000243
Figure 00000244
Figure 00000245
Figure 00000246
Figure 00000247
Figure 00000248
Figure 00000249
Figure 00000250
Figure 00000251
Figure 00000252
Figure 00000253
Figure 00000254
Figure 00000255
Figure 00000256
Figure 00000257
Figure 00000258
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000268
Figure 00000269
Figure 00000270
Figure 00000271
Figure 00000272
Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294

Claims (17)

1. Соединение формулы (I):
Figure 00000295

где А представляет собой фенил или бензофуран, каждый из которых возможно замещен по меньшей мере одним R;
R выбран из F, Cl, Br, I, -CN, -NO2, -CF3, -ОН, -OR3, -OCF3, С1-С6алкила, С3-С6циклоалкила, C1-С6галогеноалкила и фенила;
J представляет собой связь;
R1 представляет собой CO2R2, где R2 представляет собой водород;
Z представляет собой О, S или NH;
X представляет собой W-L-B или В, где В возможно замещен по меньшей мере одним R;
W представляет собой NR2, О или связь;
L представляет собой метилен, этилен, замещенный по меньшей мере одним R, С3-С6алкилен, С2-С6алкенилен или С2-С6алкинилен, где метилен, С3-С6алкилен, С2-С6алкенилен или С2-С6алкинилен возможно замещен по меньшей мере одним R;
В выбран из фурана, тиофена, пиррола, пиридина, оксазола, тиазола, имидазола, тиадиазола, бензоксазола, бензотиазола, бензимидазола, бензоксадиазола, бензотиадиазола, пиразолопиридина, индолизина, фуропиридина, тиенотиофена, хинолина и изохинолина;
каждый R3 независимо выбран из С1-С6алкила;
каждый R4 независимо выбран из водорода или С1-С6алкила; или его фармацевтически приемлемые соль, сольват или N-оксид.
2. Соединение по п.1, где R4 представляет собой водород.
3. Соединение по п.2, где Z представляет собой О.
4. Соединение по п.3, где А представляет собой фенил.
5. Соединение по п.4, где фенил замещен по меньшей мере одним R.
6. Соединение по п.5, где фенил замещен тремя R.
7. Соединение по п.6, где R выбран из F, Cl, Br, I или С1-С6алкила.
8. Соединение по п.7, где С1-С6алкил представляет собой метил, этил, н-пропил, изопропил, н-бутил, изобутил или трет-бутил.
9. Соединение по п.8, где X представляет собой В.
10. Соединение по п.9, где В выбран из бензоксазола, бензотиазола, бензимидазола, пиразолопиридина, бензоксадиазола и бензотиадиазола.
11. Соединение, выбранное из:
Figure 00000296
,
Figure 00000297
,
Figure 00000298
,
Figure 00000299
,
Figure 00000300
,
Figure 00000301
,
Figure 00000302
,
Figure 00000303
,
Figure 00000304
,
Figure 00000305
,
Figure 00000306
,
Figure 00000307
,
Figure 00000308
,
Figure 00000309
,
Figure 00000310
,
Figure 00000311
,
Figure 00000312
,
Figure 00000313
,
Figure 00000314
,
Figure 00000315
,
Figure 00000316
,
Figure 00000317
,
Figure 00000318
,
Figure 00000319
,
Figure 00000320
,
Figure 00000321
,
Figure 00000322
,
Figure 00000323
,
Figure 00000324
,
Figure 00000325
,
Figure 00000326
,
Figure 00000327
,
Figure 00000328
,
Figure 00000329
,
Figure 00000330
,
Figure 00000331
,
Figure 00000332
,
Figure 00000333
,
Figure 00000334
,
Figure 00000335
,
Figure 00000336
,
Figure 00000337
,
Figure 00000338
,
Figure 00000339
,
Figure 00000340
,
Figure 00000341
,
Figure 00000342
,
Figure 00000343
,
Figure 00000344
,
Figure 00000345
,
Figure 00000346
,
Figure 00000347
,
Figure 00000348
,
Figure 00000349
,
Figure 00000350
,
Figure 00000351
,
Figure 00000352
,
Figure 00000353
,
Figure 00000354
,
Figure 00000355
,
Figure 00000356
,
Figure 00000357
,
Figure 00000358
,
Figure 00000359
,
Figure 00000360
,
Figure 00000361
,
Figure 00000362
,
Figure 00000363
,
Figure 00000364
,
Figure 00000365
,
Figure 00000366
,
Figure 00000367
,
Figure 00000368
,
Figure 00000369
,
Figure 00000370
,
Figure 00000371
,
Figure 00000372
,
Figure 00000373
,
Figure 00000374
и
Figure 00000375
,
Figure 00000376
,
Figure 00000377
,
Figure 00000378
,
Figure 00000379
,
Figure 00000380
,
Figure 00000381
,
Figure 00000382
,
Figure 00000383
,
Figure 00000384
,
Figure 00000385
,
Figure 00000386
,
Figure 00000387
,
Figure 00000388
,
Figure 00000389
,
Figure 00000390

Figure 00000391
,
Figure 00000392
,
Figure 00000393

и
Figure 00000394
,
Figure 00000395
,
Figure 00000396
,
Figure 00000397
,
Figure 00000398
,
Figure 00000399
,
Figure 00000400
,
Figure 00000401
и
Figure 00000402
;
Figure 00000403
,
Figure 00000404
,
Figure 00000405
,
Figure 00000406
,
Figure 00000407
,
Figure 00000408
,
Figure 00000409
,
Figure 00000410
,
Figure 00000411
,
Figure 00000412
,
Figure 00000413
,
Figure 00000414

и
Figure 00000415
,
Figure 00000416
,
Figure 00000417
,
Figure 00000418
,
Figure 00000419
,
Figure 00000420
,
Figure 00000421
,
Figure 00000422
,
Figure 00000423
,
Figure 00000424
,
Figure 00000425
,
Figure 00000426
,
Figure 00000427
,
Figure 00000428
,
Figure 00000429
,
Figure 00000430
,
Figure 00000431
,
Figure 00000432
,
Figure 00000433
,
Figure 00000434
,
Figure 00000435
,
Figure 00000436
,
Figure 00000437
,
Figure 00000438
,
Figure 00000439
,
Figure 00000440
,
Figure 00000441
,
Figure 00000442
,
Figure 00000443
,
Figure 00000444
,
Figure 00000445
,
Figure 00000446
,
Figure 00000447
,
Figure 00000448
,
Figure 00000449
,
Figure 00000450
,
Figure 00000451
,
Figure 00000452
,
Figure 00000453
,
Figure 00000454
,
Figure 00000455
,
Figure 00000456
,
Figure 00000457
,
Figure 00000458
,
Figure 00000459
,
Figure 00000460
,
Figure 00000461
,
Figure 00000462
,
Figure 00000463
,
Figure 00000464
и
Figure 00000465

или его фармацевтически приемлемые соль или сольват.
12. Фармацевтическая композиция для лечения аутоиммунного заболевания, гетероиммунного заболевания или состояния либо воспалительного заболевания, содержащая соединение по п.1 и фармацевтически приемлемый разбавитель, эксципиент, носитель или связующее вещество для них.
13. Применение соединения по п.1 или его фармацевтически приемлемой соли в изготовлении лекарственного средства для лечения аутоиммунного заболевания, гетероиммунного заболевания или состояния либо воспалительного заболевания.
14. Применение по п.13, где аутоиммунное заболевание представляет собой ревматоидный артрит, рассеянный склероз, псориаз или остеоартрит.
15. Применение по п.14, где аутоиммунное заболевание представляет собой псориаз.
16. Применение по п.13, где гетероиммунное заболевание или состояние представляет собой отторжение трансплантата или отторжение органного трансплантата.
17. Применение по п.13, где воспалительное заболевание представляет собой колит.
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