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RU2016135922A - Терапевтические соединения и композиции - Google Patents

Терапевтические соединения и композиции Download PDF

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RU2016135922A
RU2016135922A RU2016135922A RU2016135922A RU2016135922A RU 2016135922 A RU2016135922 A RU 2016135922A RU 2016135922 A RU2016135922 A RU 2016135922A RU 2016135922 A RU2016135922 A RU 2016135922A RU 2016135922 A RU2016135922 A RU 2016135922A
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alkyl
heteroaryl
compound
substituted
aryl
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RU2016135922A
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RU2733405C2 (ru
RU2016135922A3 (ru
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Роберт А. ХРУСЬЦЕЛЬ
Роберт К. ГЭДВУД
Нил Дж. ХЭЙВОРД
Майкл Дж. МЕЛЬНИК
Мануэль НАВИА
Тони Дж. ПОЭЛЬ
Кэтрин А. СТЮАРТ
Франс Л. СТАССЕН
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Экзитера Фармасьютикалз Инк.
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Claims (78)

1. Соединение формулы (II):
Figure 00000001
(II),
или его фармацевтически приемлемая соль, где
R1 представляет собой H или -C1-6 алкил;
R2 представляет собой H, –C1-6 алкил, –CO2R5, –C(O)NR9R10, –CN, –CNH(OR5), –CHN(OR5) или гетероарил;
R3 представляет собой H или -C1-6 алкил;
A представляет собой связь, C1-6 алкилен, C2-6 алкинилен или C2-6 алкинилен;
R4 представляет собой циклоалкил, арил, гетероарил или гетероциклил, каждый из которых замещен 0-3 R6;
каждый R5 независимо представляет собой H, -C1-6 алкил, аралкил или арил, замещенный 0-3 -NH2 или R6;
X представляет собой –C(O)O–, –OC(O)–, –C(O)S(O)2–, –S(O)2C(O)–, –C(O)N(R5)– или –N(R5)C(O)–;
Y представляет собой циклоалкил, гетероарил или гетероциклил, каждый из которых замещен 0-3 –NH2 или R6; или замщенный -С1-6алкил или фенил, замещенный 1-2 R6;
R7 представляет собой H, –C1-6 алкил, циклоалкил, арил, гетероарил или гетероциклил, каждый из которых замещен 0-3 –NH2 или R6;
где, если R6 представляет собой заместитель для любого R4, R5 или R7, то каждый R6 независимо представляет собой галоген, гидрокси, циано, нитро, C1-6 алкил, C1-6 алкокси, -NR9R10, -NHR10, -C(O)R11, -C(O)OR11, –C(O)NR9R10, –C(NR8)(N(R8)2), –SOqR11, –SO2NR9R10, –NHC(O)OR11, –NHC(O)R11, арил, гетероарил, аралкил, циклоалкил, гетероаралкил, гетероциклил или гетероциклилалкил; или
две группы R6, взятые вместе с атомами, к которым они присоединены образуют 5-7-членное кольцо; и
если R6 является заместителем Y, то каждый R6 независимо представляет собой галоген, галогеналкокси; или
две группы R6, взятые вместе с атомами, к которым они присоединены образуют:
Figure 00000002
или
Figure 00000003
;
каждый R8 независимо представляет собой H, –C1-6 алкил, –C(O)R5, –C(O)OR5, арил, гетероарил, аралкил, гетероаралкил, гетероциклил или гетероциклилалкил;
каждый R9 и R10 независимо представляет собой –C1-6 алкил, циклоалкил, гетероциклил, арил или гетероарил, или
R9 и R10 вместе образуют необязательно замещенное 5-7-членное кольцо;
каждый R11 независимо представляет собой H, –C1-10 алкил, аралкил или арил;
q равно целому числу от 0 до 2; и
n равно целому числу от 0 до 2.
2. Соединение по п.1, где R1 представляет собой H.
3. Соединение по п.1, где R2 представляет собой –CO2R5, где R5 представляет собой H или –C1-6 алкил.
4. Соединение по п.1, где A представляет собой C1-6 алкилен.
5. Соединение по п.1, где R4 представляет собой арил или гетероарил.
6. Соединение по п.5, где R4 представляет собой 6-членный гетероарил, замещенный 0-3 -NH2 или R6.
7. Соединение по п.1, где X представляет собой –C(O)N(R5)– или –N(R5)C(O)–.
8. Соединение по п.1, где соединение формулы (II) является фармацевтически приемлемой солью.
9. Соединение по п.1, где соединение формулы (II) выбрано из соединения формулы (IIa):
Figure 00000004
(IIa),
где
R1, R2, R3, R4, R7 и Y такие, как описано для формулы (II), и
m равно целому числу от 1 до 6.
10. Соединение по п.9, где соединение формулы (II) выбрано из соединения формулы (IIb):
Figure 00000005
(Ib),
где
R1, R2, R3, R4, R7, Y и m такие, как описано для формулы (IIa).
11. Соединение по п.10, где соединение формулы (IIb) представляет собой:
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
или
Figure 00000029
.
12. Соединение по п.10, где соединение формулы (IIb) выбрано из соединения формулы (IIc):
Figure 00000030
.
13. Фармацевтическая композиция, содержащая соединение формулы (II):
Figure 00000031
(II),
или его фармацевтически приемлемая соль, где
R1 представляет собой H или -C1-6 алкил;
R2 представляет собой H, –C1-6 алкил, –CO2R5, –C(O)NR9R10, –CN, –CHN(OR5) или гетероарил;
R3 представляет собой H или -C1-6 алкил;
A представляет собой связь, C1-6 алкилен, C2-6 алкинилен или C2-6 алкинилен;
R4 представляет собой циклоалкил, арил, гетероарил или гетероциклил, каждый из которых замещен 0-3 –NH2 или R6;
каждый R5 независимо представляет собой H, -C1-6 алкил, аралкил или арил, замещенный 0-3 -NH2 или R6;
X представляет собой–C(O)O–, –OC(O)–, –C(O)S(O)2–, –S(O)2C(O)–, –C(O)N(R5)– или –N(R5)C(O)–;
Y представляет собой циклоалкил, гетероарил или гетероциклил, каждый из которых замещен 0-3 –NH2 или R6; или замещенный–C1-6 алкил или фенил, замещенный 1-2 R6;
R7 представляет собой H, –C1-6 алкил, циклоалкил, арил, гетероарил или гетероциклил, каждый из которых замещен 0-3 –NH2 или R6;
где если R6 представляет собой заместителя для любого R4, R5 или R7, то каждый R6 независимо представляет собой галоген, гидрокси, циано, нитро, C1-6 алкил, C1-6 алкокси, -NR9R10, -NHR10, -C(O)R11, -C(O)OR11, –C(O)NR9R10, –C(NR8)(N(R8)2), –SOqR11, –SO2NR9R10, –NHC(O)OR11, –NHC(O)R11, арил, гетероарил, аралкил, циклоалкил, гетероаралкил, гетероциклил или гетероциклилалкил; или
если R6 является заместителем для Y, то каждый R6 независимо представляет собой галоген, галогеналкокси; или
две R6 группы, взятые вместе с атомами, к которым они присоединены, образуют:
Figure 00000032
или
Figure 00000033
;
каждый R8 независимо представляет собой H, –C1-6 алкил, –C(O)R5, –C(O)OR5, арил, гетероарил, аралкил, гетероаралкил, гетероциклил или гетероциклилалкил;
каждый R9 и R10 независимо представляет собой –C1-6 алкил, циклоалкил, гетероциклил, арил или гетероарил, или
R9 и R10 вместе образуют необязательно замещенное 5-7-членное кольцо;
каждый R11 независимо представляет собой H, –C1-10 алкил, аралкил или арил;
q равно целому числу от 0 до 2;
n равно целому числу от 0 до 2;
и один или несколько фармацевтически приемлемых носителей.
14. Соединение по п.1, где Y представляет собой фенил, замещенный 1 раз R6.
15. Соединение по п.1, где Y представляет собой фенил, а R6 представляет собой галогеналкокси.
16. Соединение по п.1, где Y представляет собой фенил, и R6 представляет собой галоген.
17. Соединение по п.1, где Y представляет собой фенил, замещенный 2 R6.
18. Соединение по п.17, где две R6 группы, взятые вместе с атомами, к которым они присоединены, образуют:
Figure 00000032
или
Figure 00000033
.
19.Соединение по п.1, где Y представляет собой циклоалкил.
20. Соединение по п.19, где Y представляет собой циклогексил.
21. Соединение по п.1, где R7 представляет собой–C1-6 алкил, замещенный 0-3–NH2 или R6.
22. Соединение по п. 21, где R7 представляет собой метил или –CF3.
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Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9738655B2 (en) 2013-03-25 2017-08-22 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor XIa inhibitors
UY40230A (es) 2014-01-31 2023-08-15 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Macrociclos con grupos P2’ heterocíclicos como inhibidores del factor XIa y composiciones farmacéuticas que los comprenden
NO2760821T3 (ru) 2014-01-31 2018-03-10
EP3102200B1 (en) 2014-02-07 2023-04-05 Exithera Pharmaceuticals Inc. Therapeutic compounds and compositions
ES2714283T3 (es) 2014-09-04 2019-05-28 Bristol Myers Squibb Co Macrociclos de diamida que son inhibidores de FXIa
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
US10344039B2 (en) 2015-10-29 2019-07-09 Merck Sharp & Dohme Corp. Macrocyclic spirocarbamate derivatives as factor XIa inhibitors, pharmaceutically acceptable compositions and their use
EP3500556B1 (en) 2016-08-22 2023-08-02 Merck Sharp & Dohme LLC Pyridine-1-oxide derivatives and their use as factor xia inhibitors
WO2018081513A1 (en) 2016-10-31 2018-05-03 Biocryst Pharmaceuticals, Inc. Prodrugs of kallikrein inhibitors
WO2018118705A1 (en) * 2016-12-23 2018-06-28 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
BR112020016123A2 (pt) * 2018-02-07 2021-02-23 eXIthera Pharmaceuticals Inc. compostos e composições terapêuticas
WO2019185046A1 (zh) * 2018-03-30 2019-10-03 上海美悦生物科技发展有限公司 四元内酰胺类化合物及其药学用途
AU2019373237A1 (en) * 2018-10-30 2021-04-22 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
JP2022506109A (ja) * 2018-10-30 2022-01-17 エクセセーラ ファーマシューティカルズ インコーポレイテッド 治療用化合物および組成物
BR112021014956A2 (pt) * 2019-01-29 2021-09-28 Exithera Pharmaceuticals, Inc. Composições e compostos terapêuticos
WO2022060952A1 (en) * 2020-09-17 2022-03-24 Exithera Pharmaceuticals, Inc. Therapeutic compounds, compositions, and methods of use thereof
CN116782911A (zh) * 2020-09-17 2023-09-19 艾克赛特赫拉制药有限责任公司 治疗性化合物、组合物及其使用方法

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4595532A (en) * 1983-02-02 1986-06-17 University Of Notre Dame Du Lac N-(substituted-methyl)-azetidin-2-ones
US5739135A (en) 1993-09-03 1998-04-14 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein and method
SE9602263D0 (sv) * 1996-06-07 1996-06-07 Astra Ab New amino acid derivatives
US5760246A (en) 1996-12-17 1998-06-02 Biller; Scott A. Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method
AU751111B2 (en) 1998-01-26 2002-08-08 Basf Aktiengesellschaft Thrombin inhibitors
SE9802206D0 (sv) 1998-06-22 1998-06-22 Astra Pharma Inc Novel compounds
US6335324B1 (en) * 1998-06-25 2002-01-01 Bristol-Myers Squibb Co. Beta lactam compounds and their use as inhibitors of tryptase
EP1089973B1 (en) * 1998-06-25 2005-11-09 Bristol-Myers Squibb Company Amidino and guanidino azetidinone tryptase inhibitors
WO2000005204A1 (en) * 1998-07-23 2000-02-03 Shionogi & Co., Ltd. MONOCYCLIC β-LACTAM COMPOUNDS AND CHYMASE INHIBITORS CONTAINING THE SAME
GB0205527D0 (en) 2002-03-08 2002-04-24 Ferring Bv Inhibitors
PT1468697E (pt) 2003-04-14 2008-03-05 Wyeth Corp Composições contendo piperacilina e tazobactam úteis para injecção
PA8603801A1 (es) * 2003-05-27 2004-12-16 Janssen Pharmaceutica Nv Derivados de la quinazolina
WO2005018672A1 (ja) * 2003-08-22 2005-03-03 Teijin Pharma Limited キマーゼ阻害剤を有効成分として含有する薬剤
ES2305887T3 (es) * 2003-12-18 2008-11-01 Janssen Pharmaceutica Nv Derivados de pirido y pirimidopirimidinas como agentes antiproliferativos.
JO3088B1 (ar) * 2004-12-08 2017-03-15 Janssen Pharmaceutica Nv مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف
US7501404B2 (en) 2005-04-04 2009-03-10 Daimed Substituted azetidinones
PE20070171A1 (es) * 2005-06-30 2007-03-08 Boehringer Ingelheim Int GLICINAMIDAS SUSTITUIDAS CON EFECTO ANTITROMBOTICO E INHIBIDOR DEL FACTOR Xa
TW200745084A (en) 2006-03-08 2007-12-16 Astrazeneca Ab Novel compounds
EP1873157A1 (en) * 2006-06-21 2008-01-02 Bayer Schering Pharma Aktiengesellschaft Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same
CN101679406B (zh) 2007-04-10 2013-07-10 百时美施贵宝公司 用作激酶抑制剂的噻唑基化合物
AU2008265104B2 (en) * 2007-06-21 2013-09-12 Janssen Pharmaceutica Nv Indolin-2-ones and aza-indolin-2-ones
RU2353619C2 (ru) * 2007-06-28 2009-04-27 Общество С Ограниченной Ответственностью "Бионика" Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции
CN102026996B (zh) * 2008-03-13 2015-01-07 百时美施贵宝公司 作为凝血因子xia抑制剂的哒嗪衍生物
KR101853026B1 (ko) * 2008-10-22 2018-04-27 어레이 바이오파마 인크. ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５­ａ］ 피리미딘 화합물
CN102753555B (zh) 2010-02-11 2018-01-12 百时美施贵宝公司 作为因子xia抑制剂的大环类
US9352016B2 (en) 2011-03-09 2016-05-31 Csl Behring Gmbh Factor XII inhibitors for the administration with medical procedures comprising contact with artificial surfaces
EP3309148A1 (en) 2011-10-14 2018-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
BR112014024287A2 (pt) * 2012-03-27 2018-05-08 Duke University composições e métodos para a prevenção e tratamento do derrame vascular induzido por mastócitos
IL312865B2 (en) 2013-09-11 2025-06-01 Eagle Biologics Inc Liquid protein formulations containing viscosity-lowering agents
EP3102200B1 (en) 2014-02-07 2023-04-05 Exithera Pharmaceuticals Inc. Therapeutic compounds and compositions
PL2926805T3 (pl) 2014-03-31 2016-12-30 Stałe kompozycje farmaceutyczne zawierające pochodne biopteryny oraz zastosowania takich kompozycji
WO2018118705A1 (en) 2016-12-23 2018-06-28 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
BR112020016123A2 (pt) 2018-02-07 2021-02-23 eXIthera Pharmaceuticals Inc. compostos e composições terapêuticas
JP2022506109A (ja) 2018-10-30 2022-01-17 エクセセーラ ファーマシューティカルズ インコーポレイテッド 治療用化合物および組成物
AU2019373237A1 (en) 2018-10-30 2021-04-22 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
BR112021014956A2 (pt) 2019-01-29 2021-09-28 Exithera Pharmaceuticals, Inc. Composições e compostos terapêuticos

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