RU2011119990A - Циклоалкиламины в качестве ингибиторов повторного поглощения моноамина - Google Patents
Циклоалкиламины в качестве ингибиторов повторного поглощения моноамина Download PDFInfo
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- RU2011119990A RU2011119990A RU2011119990/04A RU2011119990A RU2011119990A RU 2011119990 A RU2011119990 A RU 2011119990A RU 2011119990/04 A RU2011119990/04 A RU 2011119990/04A RU 2011119990 A RU2011119990 A RU 2011119990A RU 2011119990 A RU2011119990 A RU 2011119990A
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- 0 C*(C(*)(*)*(C)N(*)*)C1(CC(C)(*)C*(C)C*(C)CC1)C(C)=O Chemical compound C*(C(*)(*)*(C)N(*)*)C1(CC(C)(*)C*(C)C*(C)CC1)C(C)=O 0.000 description 6
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Abstract
1. Соединение, имеющее структуру, соответствующую формуле (I):где n равно целому числу от 0 до 2;s равно целому числу от 1 до 3;m равно целому числу от 0 до 12, при условии, что, когда n равно 0, тогда m равно не больше 8; и когда n равно 1, тогда m равно не больше 10;Ar представляет собой член, выбранный из группы, включающей замещенный или незамещенный арил, замещенный или незамещенный гетероарил и конденсированную кольцевую систему;каждый X представляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF, OR, SR, ацил, C(O)OR, C(O)NRR, S(O)R, S(O)NRR, NRR, NRS(O)R, NRC(O)R, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,где каждый R, Rи Rпредставляет собой член, независимо выбранный из группы, включающей Н, ацил, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил и замещенный или незамещенный гетероарил,где два из R, Rи R, вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца;каждый Rи Rпредставляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF, OR, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,где Rпредставляет собой член, выбранный из группы, включающей H, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный
Claims (33)
1. Соединение, имеющее структуру, соответствующую формуле (I):
где n равно целому числу от 0 до 2;
s равно целому числу от 1 до 3;
m равно целому числу от 0 до 12, при условии, что, когда n равно 0, тогда m равно не больше 8; и когда n равно 1, тогда m равно не больше 10;
Ar представляет собой член, выбранный из группы, включающей замещенный или незамещенный арил, замещенный или незамещенный гетероарил и конденсированную кольцевую систему;
каждый X представляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF3, OR5, SR5, ацил, C(O)OR5, C(O)NR6R7, S(O)2R5, S(O)2NR6R7, NR6R7, NR6S(O)2R5, NR6C(O)R5, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,
где каждый R5, R6 и R7 представляет собой член, независимо выбранный из группы, включающей Н, ацил, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил и замещенный или незамещенный гетероарил,
где два из R5, R6 и R7, вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца;
каждый R1 и R2 представляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF3, OR8, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,
где R8 представляет собой член, выбранный из группы, включающей H, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил; и
R3 и R4 являются членами, независимо выбранными из группы, включающей Н, OR9, ацил, C(O)OR9, S(O)2R9, N=N, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил, при условии, что, когда один член из R3 и R4 представляет собой N=N, тогда другой член отсутствует,
где R9 представляет собой член, выбранный из группы, включающей Н, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил;
где по меньшей мере два из R1, R2, R3, R4 и X вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца;
по меньшей мере, один из R1, R2, R3 и R4 необязательно соединен с Ar с образованием 5-7-членного кольца;
и любая его фармацевтически приемлемая соль, сольват, энантиомер, диастереомер, рацемическая смесь, энантиомерно обогащенная смесь и энантиомерно чистая форма.
2. Соединение по п.1, где указанное соединение является хиральным.
4. Соединение по п.3, где указанное соединение имеет формулу, которая представляет собой член, выбранный из группы, включающей:
где X1 и X2 являются членами, независимо выбранными из группы, включающей Н, OR5, SR5, галоген, CN, CF3, S(O)2R5, NR6R7, NR6S(O)2R5, NR6C(O)R5, ацил, замещенный или незамещенный C1-C4алкил и замещенный или незамещенный C1-C4гетероалкил,
где по меньшей мере два из R1, R3, R4, X1 и X2, вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца.
5. Соединение по п.4, где X1 и X2 являются членами, независимо выбранными из группы, включающей Н, метил, этил, н-пропил, OH, OMe, OEt, F, Cl, CN, CH2OH, CH2OMe и CF3.
6. Соединение по п.4, где R1 представляет собой H или замещенный или незамещенный C1-C4алкил.
7. Соединение по п.4, где R3 и R4 являются членами, независимо выбранными из группы, включающей замещенный или незамещенный алкил и замещенный или незамещенный гетероалкил.
8. Соединение по п.3, где Ar представляет собой член, выбранный из группы, включающей замещенный или незамещенный фенил и замещенный или незамещенный нафтил.
9. Соединение по п.8, где Ar имеет структуру, которая представляет собой член, выбранный из группы, включающей:
где Y, Z, Y1 и Z1 являются членами, независимо выбранными из группы, включающей Н, галоген, CF3, CN, OR11, SR11, NR12R13, NR12S(O)2R11, NR12C(O)R11, S(O)2R11, ацил, C(O)OR11, C(O)NR12R13, S(O)2NR12R13, NR12S(O)2R11, NR12C(O)R11, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил, замещенный или незамещенный гетероциклоалкил,
где два из Y, Z, Y1 и Z1 вместе с атомами, с которыми они связаны, необязательно соединены с образованием 5-7-членного кольца; и
каждый R11, R12 и R13 представляет собой член, независимо выбранный из группы, включающей Н, ацил, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил, замещенный или незамещенный гетероциклоалкил,
где два из R11, R12 и R13 вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца.
10. Соединение по п.9, где Y, Z, Y1 и Z1 являются членами, независимо выбранными из группы, включающей Н, CF3, OR11, SR11, OCF3, галоген и CN.
12. Композиция, содержащая первый стереоизомер и по меньшей мере один дополнительный стереоизомер соединения по п.1, где указанный первый стереоизомер присутствует в диастереомерном избытке по меньшей мере 80% относительно указанного по меньшей мере одного дополнительного стереоизомера.
13. Фармацевтическая композиция, содержащая соединение по п.1 и фармацевтически приемлемый носитель.
14. Способ ингибирования связывания лиганда транспортера моноамина с транспортером моноамина, включающий контактирование указанного транспортера моноамина и соединения по п.1.
15. Способ ингибирования активности по меньшей мере одного транспортера моноамина, включающий контактирование указанного транспортера моноамина и соединения по п.1.
16. Способ по п.14 или 15, где указанный транспортер моноамина представляет собой член, выбранный из группы, включающей транспортер серотонина (SERT), транспортер допамина (DAT), транспортер норэпинефрина (NET) и их комбинации.
17. Способ по п.15, где указанное соединение ингибирует активность по меньшей мере двух разных транспортеров моноамина.
18. Способ ингибирования поглощения по меньшей мере одного моноамина клеткой, включающий контактирование указанной клетки и соединения по п.1.
19. Способ по п.18, где указанный моноамин представляет собой член, выбранный из группы, включающей серотонин, допамин, норэпинефрин и их комбинации.
20. Способ по п.18, где указанное соединение ингибирует поглощение по меньшей мере двух разных моноаминов.
21. Способ по п.18, где указанная клетка представляет собой нервную клетку.
22. Способ лечения депрессии путем ингибирования активности по меньшей мере одного транспортера моноамина, включающий введение субъекту-млекопитающему соединения по п.1.
23. Способ по п.22, где указанным субъектом-млекопитающим является человек.
24. Способ по п.22, где указанное соединение ингибирует указанную активность по меньшей мере двух разных транспортеров моноамина.
25. Способ лечения расстройства центральной нервной системы, включающий введение субъекту, нуждающемуся в этом, терапевтически эффективного количества соединения по п.1.
26. Способ по п.25, где указанным субъектом является человек.
27. Способ по п.25, где указанное расстройство центральной нервной системы представляет собой член, выбранный из группы, включающей депрессию, нарушение познавательной способности, фибромиалгию, боль, расстройство сна, расстройство, связанное с дефицитом внимания (ADD), расстройство дефицита внимания/гиперактивности (ADHD), синдром усталых ног, шизофрению, беспокойство, обсессивно-компульсивное расстройство, посттравматическое стрессовое расстройство, предменструальную дисфорию и нейродегенеративное заболевание.
28. Способ по п.27, где указанная депрессия представляет собой член, выбранный из группы, включающей общее депрессивное расстройство (MDD), униполярную депрессию, биполярное расстройство, сезонное аффективное расстройство (SAD) и дистимию.
29. Способ по п.27, где указанное нейродегенеративное заболевание представляет собой болезнь Паркинсона.
30. Способ по п.27, где указанное расстройство сна представляет собой синдром апноэ во сне.
31. Способ по п.27, где указанная боль представляет собой нейропатическую боль.
32. Соединение, имеющее структуру, которая представляет собой член, выбранный из группы, включающей:
где n равно целому числу от 0 до 2;
p равно целому числу от 0 до 2;
m равно целому числу от 0 до 12, при условии, что, когда n равно 0, тогда m равно не больше 8; и когда n равно 1, тогда m равно не больше 10;
Ar представляет собой член, выбранный из группы, включающей замещенный или незамещенный арил, замещенный или незамещенный гетероарил и конденсированную кольцевую систему;
каждый X представляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF3, OR5, SR5, ацил, C(O)OR5, C(O)NR6R7, S(O)2R5, S(O)2NR6R7, NR6R7, NR6S(O)2R5, NR6C(O)R5, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,
где каждый R5, R6 и R7 представляет собой член, независимо выбранный из группы, включающей Н, ацил, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил и замещенный или незамещенный гетероарил,
где два из R5, R6 и R7 вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца;
каждый R1 и R2 представляет собой член, независимо выбранный из группы, включающей Н, галоген, CN, CF3, OR8, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил,
где R8 представляет собой член, выбранный из группы, включающей Н, замещенный или незамещенный алкил, замещенный или незамещенный гетероалкил, замещенный или незамещенный арил, замещенный или незамещенный гетероарил и замещенный или незамещенный гетероциклоалкил; и
где по меньшей мере два из R1, R2 и X вместе с атомами, с которыми они связаны, необязательно соединены с образованием 3-7-членного кольца;
по меньшей мере, один из R1 и R2 необязательно соединен с Ar с образованием 5-7-членного кольца;
и любая его солевая форма, сольват, энантиомер, диастереомер, рацемическая смесь, энантиомерно обогащенная смесь и энантиомерно чистая форма.
33. Соединение по п.32, где p равно 0.
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- 2007-01-05 US US11/649,927 patent/US20070203111A1/en not_active Abandoned
- 2007-01-05 KR KR1020087019131A patent/KR101294014B1/ko active IP Right Grant
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- 2007-01-05 CN CN200780008105.XA patent/CN101394847B/zh not_active Expired - Fee Related
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US10562878B2 (en) | 2020-02-18 |
JP5432526B2 (ja) | 2014-03-05 |
RU2008132320A (ru) | 2010-02-20 |
CN101394847A (zh) | 2009-03-25 |
EP1976513A2 (en) | 2008-10-08 |
KR20080083201A (ko) | 2008-09-16 |
ZA200806145B (en) | 2010-02-24 |
EP1976513B1 (en) | 2016-08-24 |
RU2430913C2 (ru) | 2011-10-10 |
AU2007205114B2 (en) | 2012-11-08 |
WO2007081857A2 (en) | 2007-07-19 |
US20070203111A1 (en) | 2007-08-30 |
CA2636324C (en) | 2012-03-20 |
WO2007081857A3 (en) | 2007-11-08 |
JP2013209390A (ja) | 2013-10-10 |
KR101294014B1 (ko) | 2013-08-09 |
CN101394847B (zh) | 2017-05-24 |
US20100190861A1 (en) | 2010-07-29 |
IL192613A0 (en) | 2009-09-22 |
JP2009531277A (ja) | 2009-09-03 |
US8877975B2 (en) | 2014-11-04 |
US20180230120A1 (en) | 2018-08-16 |
US9868718B2 (en) | 2018-01-16 |
IL192613A (en) | 2015-11-30 |
ES2594156T3 (es) | 2016-12-16 |
US20150126511A1 (en) | 2015-05-07 |
NZ569630A (en) | 2011-09-30 |
AU2007205114A1 (en) | 2007-07-19 |
EP1976513A4 (en) | 2012-04-18 |
CA2636324A1 (en) | 2007-07-19 |
BRPI0706365A2 (pt) | 2011-03-22 |
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