RU2008141374A - Фармацевтическая композиция, содержащая по крайнер мере один ингибитор ркс и по крайней мере один ингибитор киназы jak3, предназначенная для лечения аутоиммунных нарушений - Google Patents
Фармацевтическая композиция, содержащая по крайнер мере один ингибитор ркс и по крайней мере один ингибитор киназы jak3, предназначенная для лечения аутоиммунных нарушений Download PDFInfo
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- RU2008141374A RU2008141374A RU2008141374/15A RU2008141374A RU2008141374A RU 2008141374 A RU2008141374 A RU 2008141374A RU 2008141374/15 A RU2008141374/15 A RU 2008141374/15A RU 2008141374 A RU2008141374 A RU 2008141374A RU 2008141374 A RU2008141374 A RU 2008141374A
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- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 title claims abstract 8
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 title claims abstract 8
- 229940043355 kinase inhibitor Drugs 0.000 title claims abstract 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 title claims abstract 8
- 239000003112 inhibitor Substances 0.000 title claims abstract 6
- 208000023275 Autoimmune disease Diseases 0.000 title claims 4
- 238000011282 treatment Methods 0.000 title claims 4
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract 12
- 150000001875 compounds Chemical class 0.000 claims abstract 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract 10
- 210000004027 cell Anatomy 0.000 claims abstract 5
- 230000001419 dependent effect Effects 0.000 claims abstract 4
- 230000035755 proliferation Effects 0.000 claims abstract 4
- 239000012453 solvate Substances 0.000 claims abstract 4
- AXRCEOKUDYDWLF-UHFFFAOYSA-N 3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C(C1=CC=CC=C11)=CN1C(CC1)CCN1CC1=CC=CC=N1 AXRCEOKUDYDWLF-UHFFFAOYSA-N 0.000 claims abstract 2
- RELJBNLDXPSLLS-UHFFFAOYSA-N 3-(1-methylindol-3-yl)-4-(1-piperidin-4-ylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C(C1=CC=CC=C11)=CN1C1CCNCC1 RELJBNLDXPSLLS-UHFFFAOYSA-N 0.000 claims abstract 2
- KLSCBNKMNKJFBO-UHFFFAOYSA-N 3-[3-(4,7-diazaspiro[2.5]octan-7-yl)isoquinolin-1-yl]-4-(7-methyl-1h-indol-3-yl)pyrrole-2,5-dione Chemical compound C=1NC=2C(C)=CC=CC=2C=1C(C(NC1=O)=O)=C1C(C1=CC=CC=C1C=1)=NC=1N(C1)CCNC21CC2 KLSCBNKMNKJFBO-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims abstract 2
- 241000243251 Hydra Species 0.000 claims abstract 2
- 108010002350 Interleukin-2 Proteins 0.000 claims abstract 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims abstract 2
- 210000005087 mononuclear cell Anatomy 0.000 claims abstract 2
- 210000005259 peripheral blood Anatomy 0.000 claims abstract 2
- 239000011886 peripheral blood Substances 0.000 claims abstract 2
- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 3
- 210000000056 organ Anatomy 0.000 claims 3
- 210000001519 tissue Anatomy 0.000 claims 3
- 238000011321 prophylaxis Methods 0.000 claims 2
- -1 CP-690550 compound Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
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Abstract
1. Фармацевтическая комбинация, включающая ! а) по крайней мере один ингибитор РКС и ! б) по крайней мере один ингибитор киназы JAK3. ! 2. Фармацевтическая комбинация по п.1, где агентом а) является ингибитор РКС, который выбирают из соединений формул I и II, как описано в данном контексте, фармацевтически приемлемой соли или гидрата указанных соединений, соединения формулы III, как описано в данном контексте, фармацевтически приемлемой соли, гидрата или сольвата указанных соединений. ! 3. Фармацевтическая комбинация по п.1 или 2, где агентом б) является ингибитор киназы JAK3, величина IC50 которого составляет <5 мкМ по данным анализа ИЛ-2-зависимой пролиферации с использованием клеток CTL/L и НТ и по данным анализа ИЛ-2-зависимой пролиферации с использованием моноядерных клеток периферической крови человека. ! 4. Фармацевтическая комбинация по п.1, где агент б) выбирают из соединений формул IV-VII, как описано в данном контексте, или их фармацевтически приемлемой соли. ! 5. Фармацевтическая комбинация по п.1, где агентом а) является 3-(1.Н.-индол-3-ил)-4-[2-(4-метилпиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-дион, 3-(1.Н.-индол-3-ил)-4-[2-(пиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-дион, 3-[3-(4,7-диазаспиро[2.5]окт-7-ил)изохинолин-1-ил]-4-(7-метил-1Н-индол-3-ил)пиррол-2,5-дион в свободной форме или в форме их фармацевтически приемлемой соли, или гидрата, 3-(1метил-1Н-индол-3-ил)-4-[1-{(1-пиридин-2-илметил)пиперидин-4-ил}-1Н-индол-3-ил]пиррол-2,5-дион или 3-(1-метил-1Н-индол-3-ил)-4-[1-(пиперидин-4-ил)-1Н-индол-3-ил]пиррол-2,5-дион или их фармацевтически приемлемая соль, гидрат или сольват, и где предпочтительно агентом а) является ацетат 3-(1.Н.-индол-3-ил)-4-[2-(4-метилпиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-дион�
Claims (10)
1. Фармацевтическая комбинация, включающая
а) по крайней мере один ингибитор РКС и
б) по крайней мере один ингибитор киназы JAK3.
2. Фармацевтическая комбинация по п.1, где агентом а) является ингибитор РКС, который выбирают из соединений формул I и II, как описано в данном контексте, фармацевтически приемлемой соли или гидрата указанных соединений, соединения формулы III, как описано в данном контексте, фармацевтически приемлемой соли, гидрата или сольвата указанных соединений.
3. Фармацевтическая комбинация по п.1 или 2, где агентом б) является ингибитор киназы JAK3, величина IC50 которого составляет <5 мкМ по данным анализа ИЛ-2-зависимой пролиферации с использованием клеток CTL/L и НТ и по данным анализа ИЛ-2-зависимой пролиферации с использованием моноядерных клеток периферической крови человека.
4. Фармацевтическая комбинация по п.1, где агент б) выбирают из соединений формул IV-VII, как описано в данном контексте, или их фармацевтически приемлемой соли.
5. Фармацевтическая комбинация по п.1, где агентом а) является 3-(1.Н.-индол-3-ил)-4-[2-(4-метилпиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-дион, 3-(1.Н.-индол-3-ил)-4-[2-(пиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-дион, 3-[3-(4,7-диазаспиро[2.5]окт-7-ил)изохинолин-1-ил]-4-(7-метил-1Н-индол-3-ил)пиррол-2,5-дион в свободной форме или в форме их фармацевтически приемлемой соли, или гидрата, 3-(1метил-1Н-индол-3-ил)-4-[1-{(1-пиридин-2-илметил)пиперидин-4-ил}-1Н-индол-3-ил]пиррол-2,5-дион или 3-(1-метил-1Н-индол-3-ил)-4-[1-(пиперидин-4-ил)-1Н-индол-3-ил]пиррол-2,5-дион или их фармацевтически приемлемая соль, гидрат или сольват, и где предпочтительно агентом а) является ацетат 3-(1.Н.-индол-3-ил)-4-[2-(4-метилпиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-диона.
6. Фармацевтическая комбинация по п.1 или 5, где ингибитором киназы JAK3 б) является 3-{(3R,4R)-4-метил-3-[метил(7Н-пирроло[2,3-d]пиримидин-4-ил)амино]пиперидин-1-ил}-3-оксопропионитрил или соединение формулы XVII, как определено в п.5, в свободной форме или в форме фармацевтически приемлемой соли.
7. Фармацевтическая комбинация по п.1 или 5, где ингибитором киназы JAK3 б) является соединение СР-690550 в свободной форме или в форме фармацевтически приемлемой соли.
8. Фармацевтическая комбинация по п.1 для применения в способе, предназначенном для лечения или профилактики аутоиммунного заболевания или нарушения или отторжения трансплантата клетки, ткани или органа.
9. Фармацевтическая комбинация по п.1 для применения при получении лекарственного средства или набора, предназначенного для лечения или профилактики аутоиммунного заболевания или нарушения или отторжения трансплантата клетки, ткани или органа.
10. Способ лечения или профилактики аутоиммунного заболевания или нарушения или отторжения трансплантата клетки, ткани или органа у субъекта, нуждающегося в таком лечении, и указанный способ заключается в совместном введении указанному субъекту, например, одновременно или последовательно терапевтически эффективного количества по крайней мере одного ингибитора РКС и по крайней мере одного ингибитора киназы JAK3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0605691.5A GB0605691D0 (en) | 2006-03-21 | 2006-03-21 | Organic Compounds |
| GB0605691.5 | 2006-03-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2008141374A true RU2008141374A (ru) | 2010-04-27 |
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ID=36383916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008141374/15A RU2008141374A (ru) | 2006-03-21 | 2007-03-19 | Фармацевтическая композиция, содержащая по крайнер мере один ингибитор ркс и по крайней мере один ингибитор киназы jak3, предназначенная для лечения аутоиммунных нарушений |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20090062301A1 (ru) |
| EP (1) | EP2004178A1 (ru) |
| JP (1) | JP2009530331A (ru) |
| KR (1) | KR20080105093A (ru) |
| CN (1) | CN101400346A (ru) |
| AU (1) | AU2007228997A1 (ru) |
| BR (1) | BRPI0708938A2 (ru) |
| CA (1) | CA2644207A1 (ru) |
| GB (1) | GB0605691D0 (ru) |
| MX (1) | MX2008011965A (ru) |
| RU (1) | RU2008141374A (ru) |
| WO (1) | WO2007107318A1 (ru) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ563454A (en) | 2005-06-08 | 2011-03-31 | Rigel Pharmaceuticals Inc | 2,4-diaminopyrimidine derivatives for inhibition of the JAK pathway |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| GB0613162D0 (en) * | 2006-06-30 | 2006-08-09 | Novartis Ag | Organic compounds |
| US20100179175A1 (en) * | 2006-08-23 | 2010-07-15 | Sivak Jeremy M | Use of pkc inhibitors in ocular diseases |
| JP2010512335A (ja) * | 2006-12-07 | 2010-04-22 | ノバルティス アーゲー | 移植におけるpkc阻害剤の使用 |
| US20120040955A1 (en) | 2009-04-14 | 2012-02-16 | Richard John Harrison | Fluoro substituted pyrimidine compounds as jak3 inhibitors |
| EP2421867B1 (en) | 2009-04-20 | 2015-09-02 | Auspex Pharmaceuticals, Llc | Piperidine inhibitors of janus kinase 3 |
| CN106420756A (zh) * | 2009-07-28 | 2017-02-22 | 里格尔药品股份有限公司 | 抑制jak途径的组合物和方法 |
| CA2771675A1 (en) | 2009-09-11 | 2011-03-17 | Cellzome Limited | Ortho substituted pyrimidine compounds as jak inhibitors |
| CA2775009A1 (en) | 2009-10-20 | 2011-04-28 | Cellzome Limited | Heterocyclyl pyrazolopyrimidine analogues as jak inhibitors |
| SG184989A1 (en) | 2010-04-30 | 2012-11-29 | Cellzome Ltd | Pyrazole compounds as jak inhibitors |
| WO2012000970A1 (en) | 2010-07-01 | 2012-01-05 | Cellzome Limited | Triazolopyridines as tyk2 inhibitors |
| JP2013534233A (ja) | 2010-08-20 | 2013-09-02 | セルゾーム リミティッド | 選択的jak阻害剤としてのヘテロシクリルピラゾロピリミジン類似体 |
| KR101317492B1 (ko) * | 2010-09-29 | 2013-10-15 | 가톨릭대학교 산학협력단 | Ag490을 유효성분으로 포함하는 면역질환의 예방 또는 치료용 조성물 |
| US9198911B2 (en) | 2010-11-02 | 2015-12-01 | The Trustees Of Columbia University In The City Of New York | Methods for treating hair loss disorders |
| CA2815330A1 (en) | 2010-11-09 | 2012-05-18 | Cellzome Limited | Pyridine compounds and aza analogues thereof as tyk2 inhibitors |
| WO2012143320A1 (en) | 2011-04-18 | 2012-10-26 | Cellzome Limited | (7h-pyrrolo[2,3-d]pyrimidin-2-yl)amine compounds as jak3 inhibitors |
| UY34072A (es) | 2011-05-17 | 2013-01-03 | Novartis Ag | Derivados sustituidos de indol |
| KR20140047092A (ko) | 2011-07-28 | 2014-04-21 | 셀좀 리미티드 | Jak 억제제로서의 헤테로시클릴 피리미딘 유사체 |
| WO2013017479A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| WO2013017480A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| EP2760863A1 (en) | 2011-09-20 | 2014-08-06 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as kinase inhibitors |
| CN104169272A (zh) | 2011-12-23 | 2014-11-26 | 赛尔佐姆有限公司 | 作为激酶抑制剂的嘧啶-2,4-二胺衍生物 |
| SG11201405761WA (en) | 2012-03-16 | 2014-10-30 | Axikin Pharmaceuticals Inc | 3,5-diaminopyrazole kinase inhibitors |
| HRP20181976T1 (hr) * | 2012-03-29 | 2019-01-25 | The Trustees Of Columbia University In The City Of New York | Postupci za liječenje poremećaja gubitka kose |
| US9296725B2 (en) | 2012-05-24 | 2016-03-29 | Cellzome Limited | Heterocyclyl pyrimidine analogues as TYK2 inhibitors |
| AU2014216178B2 (en) | 2013-02-15 | 2018-06-28 | KALA BIO, Inc. | Therapeutic compounds and uses thereof |
| CN105189462B (zh) | 2013-02-20 | 2017-11-10 | 卡拉制药公司 | 治疗性化合物和其用途 |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| CN103232444B (zh) * | 2013-04-18 | 2015-07-22 | 中国人民解放军军事医学科学院微生物流行病研究所 | 萘酚喹衍生物及其制备和其应用 |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| AU2014342042B2 (en) | 2013-11-01 | 2017-08-17 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| EA032473B1 (ru) | 2014-12-23 | 2019-05-31 | Аксикин Фармасьютикалз, Инк. | 3,5-диаминопиразоловые ингибиторы киназы |
| CA3036340A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| EP3509422A4 (en) | 2016-09-08 | 2020-05-20 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
| CN109688818A (zh) | 2016-09-08 | 2019-04-26 | 卡拉制药公司 | 治疗化合物的晶型及其用途 |
| CN108992454B (zh) * | 2018-06-20 | 2020-06-02 | 合肥医工医药股份有限公司 | 一种治疗皮肤炎症性疾病的复方药物组合物 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5545636A (en) * | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| EP0817627B1 (en) * | 1993-12-23 | 2005-03-09 | Eli Lilly And Company | Protein kinase c inhibitors |
| US5491242A (en) * | 1994-06-22 | 1996-02-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| PT1382339E (pt) * | 1999-12-10 | 2008-02-06 | Pfizer Prod Inc | Composições que contêm derivados de pirrolo[2,3-d]- pirimidina |
| EP1275646A4 (en) * | 2000-03-30 | 2003-05-28 | Sagami Chem Res | INDOLYLPYRROL DERIVATIVES AND CELL DEATH INHIBITORS |
| ES2257410T3 (es) * | 2000-06-26 | 2006-08-01 | Pfizer Products Inc. | Compuestos de pirrolo(2,3-d)pirimidina como agentes inmunosupresores. |
| DE60140201D1 (en) * | 2000-11-07 | 2009-11-26 | Novartis Ag | Indolylmaleimidderivative als proteinkinase-c-inhibitoren |
| US7301023B2 (en) * | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| GT200200234A (es) * | 2001-12-06 | 2003-06-27 | Compuestos cristalinos novedosos | |
| TWI324064B (en) * | 2002-04-03 | 2010-05-01 | Novartis Ag | Indolylmaleimide derivatives |
| WO2005060972A2 (en) * | 2003-12-17 | 2005-07-07 | Pfizer Products Inc. | Pyrrolo [2,3-d] pyrimidine compounds for treating transplant rejection |
| MX2007006204A (es) * | 2004-11-24 | 2007-06-20 | Novartis Ag | Combinaciones que comprenden inhibidores de jak y cuando menos uno de entre inhibidores de bcr-abl, flt-3, fak o raf cinasa. |
-
2006
- 2006-03-21 GB GBGB0605691.5A patent/GB0605691D0/en not_active Ceased
-
2007
- 2007-03-19 WO PCT/EP2007/002416 patent/WO2007107318A1/en not_active Ceased
- 2007-03-19 MX MX2008011965A patent/MX2008011965A/es not_active Application Discontinuation
- 2007-03-19 BR BRPI0708938-4A patent/BRPI0708938A2/pt not_active IP Right Cessation
- 2007-03-19 KR KR1020087022904A patent/KR20080105093A/ko not_active Withdrawn
- 2007-03-19 CA CA002644207A patent/CA2644207A1/en not_active Abandoned
- 2007-03-19 JP JP2009500756A patent/JP2009530331A/ja active Pending
- 2007-03-19 US US12/282,416 patent/US20090062301A1/en not_active Abandoned
- 2007-03-19 EP EP07723383A patent/EP2004178A1/en not_active Withdrawn
- 2007-03-19 RU RU2008141374/15A patent/RU2008141374A/ru not_active Application Discontinuation
- 2007-03-19 CN CNA2007800087427A patent/CN101400346A/zh active Pending
- 2007-03-19 AU AU2007228997A patent/AU2007228997A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007107318A1 (en) | 2007-09-27 |
| MX2008011965A (es) | 2008-10-01 |
| GB0605691D0 (en) | 2006-05-03 |
| CN101400346A (zh) | 2009-04-01 |
| CA2644207A1 (en) | 2007-09-27 |
| BRPI0708938A2 (pt) | 2011-06-14 |
| JP2009530331A (ja) | 2009-08-27 |
| EP2004178A1 (en) | 2008-12-24 |
| KR20080105093A (ko) | 2008-12-03 |
| US20090062301A1 (en) | 2009-03-05 |
| AU2007228997A1 (en) | 2007-09-27 |
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| Date | Code | Title | Description |
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| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20110513 |