RU2014145682A - Органические соединения - Google Patents
Органические соединения Download PDFInfo
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- RU2014145682A RU2014145682A RU2014145682A RU2014145682A RU2014145682A RU 2014145682 A RU2014145682 A RU 2014145682A RU 2014145682 A RU2014145682 A RU 2014145682A RU 2014145682 A RU2014145682 A RU 2014145682A RU 2014145682 A RU2014145682 A RU 2014145682A
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- 150000002894 organic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 41
- 150000003839 salts Chemical group 0.000 claims abstract 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 11
- 238000000034 method Methods 0.000 claims abstract 8
- 201000000980 schizophrenia Diseases 0.000 claims abstract 6
- 208000019116 sleep disease Diseases 0.000 claims abstract 6
- 208000012902 Nervous system disease Diseases 0.000 claims abstract 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract 4
- 208000019901 Anxiety disease Diseases 0.000 claims abstract 3
- 208000008589 Obesity Diseases 0.000 claims abstract 3
- 208000028017 Psychotic disease Diseases 0.000 claims abstract 3
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 claims abstract 3
- 230000036506 anxiety Effects 0.000 claims abstract 3
- 239000003085 diluting agent Substances 0.000 claims abstract 3
- 235000020824 obesity Nutrition 0.000 claims abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 3
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims abstract 2
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract 2
- 208000015114 central nervous system disease Diseases 0.000 claims abstract 2
- 239000001530 fumaric acid Substances 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims 11
- 238000013019 agitation Methods 0.000 claims 8
- 208000035475 disorder Diseases 0.000 claims 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims 8
- 206010012289 Dementia Diseases 0.000 claims 5
- 208000024827 Alzheimer disease Diseases 0.000 claims 4
- 208000020706 Autistic disease Diseases 0.000 claims 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims 4
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 3
- 206010003805 Autism Diseases 0.000 claims 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 2
- 206010019233 Headaches Diseases 0.000 claims 2
- 208000030990 Impulse-control disease Diseases 0.000 claims 2
- 208000019695 Migraine disease Diseases 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 229960003638 dopamine Drugs 0.000 claims 2
- 230000001667 episodic effect Effects 0.000 claims 2
- 231100000869 headache Toxicity 0.000 claims 2
- 230000004899 motility Effects 0.000 claims 2
- 230000037361 pathway Effects 0.000 claims 2
- 208000028173 post-traumatic stress disease Diseases 0.000 claims 2
- 208000020016 psychiatric disease Diseases 0.000 claims 2
- 229940076279 serotonin Drugs 0.000 claims 2
- 230000000697 serotonin reuptake Effects 0.000 claims 2
- 208000012201 sexual and gender identity disease Diseases 0.000 claims 2
- 208000015891 sexual disease Diseases 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 208000006264 Korsakoff syndrome Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 1
- 208000024777 Prion disease Diseases 0.000 claims 1
- 206010039966 Senile dementia Diseases 0.000 claims 1
- 201000004810 Vascular dementia Diseases 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 230000001771 impaired effect Effects 0.000 claims 1
- 208000027061 mild cognitive impairment Diseases 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- 201000010099 disease Diseases 0.000 abstract 1
- 230000000926 neurological effect Effects 0.000 abstract 1
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- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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Abstract
1. Соединение формулы I:где:X представляет собой N(H), N(Салкил) или О;Rпредставляет собой Н или Салкил (например, метил);Rпредставляет собой Н или OR, где Rпредставляет собой Н или Салкил (например, метил);при условии, что Rи Rоба не представляют собой Н, и Rи Rоба не представляют собой Н;в свободной форме или в форме соли.2. Соединение по п. 1, где Rпредставляет собой OR.3. Соединение по п. 2, где Rпредставляет собой Салкил.4. Соединение по п. 3, где Rпредставляет собой метил.5. Соединение по п. 1, где Rпредставляет собой ORи Rпредставляет собой Cалкил.6. Соединение по п. 5, где Rпредставляет собой ORи Rпредставляет собой метил.7. Соединение по п. 1, где X представляет собой N(Салкил).8. Соединение по п. 1, где X представляет собой О.9. Соединение по п. 1, где X представляет собой N(H).10. Соединение по п. 7, где X представляет собой N(CH);11. Соединение по п. 1, которое представляет собой:в свободной форме или в форме соли.12. Соединение по п. 1, которое представляет собой:в свободной форме или в форме соли.13. Соединение по п. 1, где указанное соединение находится в форме соли.14. Соединение по п. 13, где соль выбирают из группы, состоящей из толуолсульфоновой, фумаровой и фосфорной кислотно-аддитивной соли.15. Фармацевтическая композиция, содержащая соединение по п. 1, в комбинации или ассоциации с фармацевтически приемлемым разбавителем или носителем.16. Способ лечения или профилактики нарушения центральной нервной системы, включающий введение нуждающемуся в этом пациенту соединения по п. 1.17. Способ по п. 16, где указанное нарушение выбирают из группы, состоящей из ожирения, тревоги, депрессии (например, рефракторной депрессии и MDD), психоза, шизофрении, нарушений сна (в частности, нарушений сна, связанных с шизофренией и другими психиатрическими и неврологическими заболева
Claims (27)
1. Соединение формулы I:
где:
X представляет собой N(H), N(С1-4алкил) или О;
R1 представляет собой Н или С1-6алкил (например, метил);
R2 представляет собой Н или OR3, где R3 представляет собой Н или С1-6алкил (например, метил);
при условии, что R1 и R2 оба не представляют собой Н, и R1 и R3 оба не представляют собой Н;
в свободной форме или в форме соли.
2. Соединение по п. 1, где R2 представляет собой OR3.
3. Соединение по п. 2, где R1 представляет собой С1-6алкил.
4. Соединение по п. 3, где R1 представляет собой метил.
5. Соединение по п. 1, где R2 представляет собой OR3 и R3 представляет собой C1-6алкил.
6. Соединение по п. 5, где R2 представляет собой OR3 и R3 представляет собой метил.
7. Соединение по п. 1, где X представляет собой N(С1-4алкил).
8. Соединение по п. 1, где X представляет собой О.
9. Соединение по п. 1, где X представляет собой N(H).
10. Соединение по п. 7, где X представляет собой N(CH3);
13. Соединение по п. 1, где указанное соединение находится в форме соли.
14. Соединение по п. 13, где соль выбирают из группы, состоящей из толуолсульфоновой, фумаровой и фосфорной кислотно-аддитивной соли.
15. Фармацевтическая композиция, содержащая соединение по п. 1, в комбинации или ассоциации с фармацевтически приемлемым разбавителем или носителем.
16. Способ лечения или профилактики нарушения центральной нервной системы, включающий введение нуждающемуся в этом пациенту соединения по п. 1.
17. Способ по п. 16, где указанное нарушение выбирают из группы, состоящей из ожирения, тревоги, депрессии (например, рефракторной депрессии и MDD), психоза, шизофрении, нарушений сна (в частности, нарушений сна, связанных с шизофренией и другими психиатрическими и неврологическими заболеваниями), половых расстройств, мигрени, состояний, связанных с головной болью, социофобий, возбуждения, возбуждения при деменции (например, возбуждения при болезни Альцгеймера), возбуждения при аутизме и родственных аутистических нарушениях, нарушений желудочно-кишечного тракта, таких как нарушение функции моторики желудочно-кишечного тракта, посттравматического стресса, расстройства контроля над побуждениями, синдрома эпизодического нарушения контроля.
18. Способ по п. 16, где указанное нарушение представляет собой одно или несколько нарушений, связанных с деменцией, например, нарушения, связанные с легким когнитивным дефицитом, и дементные заболевания, включая сенильную деменцию, болезнь Альцгеймера, болезнь Пика, лобно-височную деменцию, парасупрануклеарный паралич, деменцию с тельцами Леви, сосудистую деменцию, болезнь Гентингтона, болезнь Паркинсона, рассеянный склероз, амиотрофический боковой склероз, синдром Дауна, старческую депрессию, синдром Вернике-Корсакова, кортикобазальную дегенерацию и прионную болезнь.
19. Способ по п. 16, где указанное нарушение представляет собой нарушение, в которое вовлечен путь серотонинового 5-HT2A, дофаминового D2 и/или переносчика обратного захвата серотонина (SERT).
20. Соединение формулы I:
где:
X представляет собой N(H) или N(С1-4алкил);
R1 представляет собой Н или С1-6алкил (например, метил);
R2 представляет собой OR3, где R3 представляет собой Н или C1-6алкил (например, метил);
при условии, что R1 и R3 оба не представляют собой Н;
в свободной форме или в форме соли.
21. Соединение по п. 20, где X представляет собой N(C1-4алкил).
22. Соединение по п. 21, где X представляет собой N(метил).
23. Соединение по п. 20, где R3 представляет собой C1-6алкил (например, метил).
24. Соединение по п. 20, где R3 представляет собой Н.
25. Фармацевтическая композиция, содержащая соединение по п. 20, в комбинации или ассоциации с фармацевтически приемлемым разбавителем или носителем.
26. Способ лечения или профилактики нарушения, выбранного из группы, состоящей из ожирения, тревоги, депрессии (например, рефракторной депрессии и MDD), психоза, шизофрении, нарушений сна (в частности, нарушений сна, связанных с шизофренией и другими психиатрическими и неврологическими заболеваниями), половых расстройств, мигрени, состояний, связанных с головной болью, социофобий, возбуждения, возбуждения при деменции (например, возбуждения при болезни Альцгеймера), возбуждения при аутизме и родственных аутистических нарушениях, нарушений желудочно-кишечного тракта, таких как нарушение функции моторики желудочно-кишечного тракта, посттравматического стресса, расстройства контроля над побуждениями, синдрома эпизодического нарушения контроля, включающий введение нуждающемуся в этом пациенту соединения по п. 20.
27. Способ по п. 26, где указанное нарушение представляет собой нарушение, в которое вовлечен путь серотонинового 5-НТ2А, дофаминового D2 и/или переносчика обратного захвата серотонина (SERT).
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261624292P | 2012-04-14 | 2012-04-14 | |
| US201261624291P | 2012-04-14 | 2012-04-14 | |
| US201261624293P | 2012-04-14 | 2012-04-14 | |
| US61/624,292 | 2012-04-14 | ||
| US61/624,291 | 2012-04-14 | ||
| US61/624,293 | 2012-04-14 | ||
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| JP2017509686A (ja) | 2014-04-04 | 2017-04-06 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 有機化合物 |
| WO2015191554A1 (en) | 2014-06-09 | 2015-12-17 | Intra-Cellular Therapies, Inc. | Compounds and methods of use to treat schizophrenia |
| MX385678B (es) | 2016-01-26 | 2025-03-18 | Intra Cellular Therapies Inc | Gamma-carbolinas heterocíclicas fusionadas sustituidas, composiciones farmacéuticas y métodos de uso. |
| IL297676B2 (en) | 2016-03-25 | 2023-12-01 | Intra Cellular Therapies Inc | A controlled or delayed release pharmaceutical preparation containing a deuterated compound |
| JP2019513143A (ja) | 2016-03-28 | 2019-05-23 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 新規塩類および結晶 |
| EP3525763B1 (en) | 2016-10-12 | 2025-03-05 | Intra-Cellular Therapies, Inc. | Amorphous solid dispersions |
| IL304026B2 (en) | 2017-03-24 | 2024-11-01 | Intra Cellular Therapies Inc | A pharmaceutical preparation containing 1-(4-fluoro-phenyl)-4-((Sa10,Rb6)-3-D2-2,2-methyl-2, 3, a10, 10, 9, b6- hexahydro-H7, H1- Pyrido[3',4',:4,5]pyrrolo[3,2,1-de]quioxalin-8-yl)-butan-1-one and its uses |
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| JP7223742B2 (ja) | 2017-07-26 | 2023-02-16 | イントラ-セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
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2013
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- 2013-04-14 EP EP20190036.2A patent/EP3791879A1/en active Pending
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- 2013-04-14 KR KR1020147031752A patent/KR20140146192A/ko not_active Withdrawn
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