KR20160106622A - 화합물 - Google Patents
화합물 Download PDFInfo
- Publication number
- KR20160106622A KR20160106622A KR1020167020367A KR20167020367A KR20160106622A KR 20160106622 A KR20160106622 A KR 20160106622A KR 1020167020367 A KR1020167020367 A KR 1020167020367A KR 20167020367 A KR20167020367 A KR 20167020367A KR 20160106622 A KR20160106622 A KR 20160106622A
- Authority
- KR
- South Korea
- Prior art keywords
- mmol
- pharmaceutically acceptable
- methyl
- group
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018155916A3 (ko) * | 2017-02-22 | 2018-12-06 | 재단법인 대구경북첨단의료산업진흥재단 | 피롤로-피리미딘 유도체 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| WO2020036437A1 (ko) * | 2018-08-16 | 2020-02-20 | 재단법인 대구경북첨단의료산업진흥재단 | 치환된 헤테로아릴 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10339791B2 (en) | 2007-06-12 | 2019-07-02 | Icontrol Networks, Inc. | Security network integrated with premise security system |
| WO2017156493A1 (en) | 2016-03-11 | 2017-09-14 | Denali Therapeutics Inc. | Compounds, compositions, and methods |
| UA118369C2 (uk) | 2014-01-29 | 2019-01-10 | Глаксосмітклайн Інтеллектьюел Проперті Девелопмент Лімітед | Сполуки, що інгібують активність lrrk2 кінази |
| WO2015113451A1 (en) | 2014-01-29 | 2015-08-06 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
| CN105153131B (zh) * | 2015-09-21 | 2017-10-17 | 马彦丽 | 一种在护理上治疗人神经胶质瘤的药物组合物 |
| CN105348270B (zh) * | 2015-11-09 | 2018-01-09 | 吕显艳 | 一种防治牙体牙髓感染的药物组合物 |
| WO2017087905A1 (en) * | 2015-11-20 | 2017-05-26 | Denali Therapeutics Inc. | Compound, compositions, and methods |
| US10023579B2 (en) | 2015-12-16 | 2018-07-17 | Southern Research Institute | Pyrrolopyrimidine compounds, use as inhibitors of the kinase LRRK2, and methods for preparation thereof |
| CN105418616B (zh) * | 2015-12-26 | 2018-01-12 | 山东大学 | 一种含有 4‑氨基吡唑结构的jak 激酶抑制剂及其制备方法和应用 |
| SG10201912632YA (en) | 2016-06-16 | 2020-02-27 | Denali Therapeutics Inc | Pyrimidin-2-ylamino-1h-pyrazols as lrrk2 inhibitors for use in the treatment of neurodegenerative disorders |
| EP3573956A4 (en) * | 2017-01-25 | 2020-08-12 | GlaxoSmithKline Intellectual Property Management Limited | LINKS |
| RU2730849C1 (ru) | 2017-03-23 | 2020-08-26 | Даегу-Гиеонгбук Медикал Инновейшн Фаундейшн | Производное пирроло-пиридинового соединения, способ его получения и фармацевтическая композиция, содержащая его в качестве активного ингредиента, для профилактики и лечения заболеваний, связанных с протеинкиназой |
| EP3722298B1 (en) * | 2017-12-05 | 2023-08-02 | Oscotec Inc. | Pyrrolo(pyrazolo)pyrimidine derivative as lrrk2 inhibitor |
| CN108715834B (zh) * | 2018-06-01 | 2021-09-14 | 天晴干细胞股份有限公司 | 一种富含cd41+、cd81+微囊的血小板裂解液制备方法 |
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| KR20200090637A (ko) | 2019-01-18 | 2020-07-29 | 보로노이바이오 주식회사 | 피롤로피리딘 유도체 및 단백질 키나아제 관련 질환의 예방 또는 치료에서의 사용을 위한 이의 용도 |
| CZ308800B6 (cs) * | 2019-02-12 | 2021-05-26 | Univerzita Palackého v Olomouci | Heterocyklické dusíkaté deriváty purinu, farmaceutické přípravky obsahující tyto deriváty a jejich použití při neuroprotekci |
| AU2021371697B2 (en) * | 2020-10-29 | 2024-10-24 | Suzhou Yabao Pharmaceutical R&D Co., Ltd. | Substituted diarylamine compound, pharmaceutical composition thereof, preparation method therefor, and use thereof |
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| EP4422750A1 (en) | 2021-10-27 | 2024-09-04 | H. Lundbeck A/S | Lrrk2 inhibitors |
| WO2023076404A1 (en) | 2021-10-27 | 2023-05-04 | Aria Pharmaceuticals, Inc. | Methods for treating systemic lupus erythematosus |
| WO2024056775A1 (en) | 2022-09-15 | 2024-03-21 | H. Lundbeck A/S | Macrocyclic leucine-rich repeat kinase 2 (lrrk2) inhibitors |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004274403A1 (en) | 2003-09-03 | 2005-03-31 | Aventis Pharmaceuticals Inc. | 5-aryl-Pyrazolo(4,3-d)pyrimidines, pyridines, and pyrazines and related compounds |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| EP2316927B1 (en) | 2004-10-21 | 2014-11-05 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Kaspp (lrrk2) gene, its production and use for the detection and treatment of neurodegenerative disorders |
| WO2006050076A1 (en) | 2004-10-29 | 2006-05-11 | Janssen Pharmaceutica, N.V. | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
| NO323175B1 (no) | 2004-12-23 | 2007-01-15 | Jan O Aasly | Framgangsmate for a pavise en mutasjon som forarsaker arvelig parkinsonisme |
| EP1948658A1 (en) | 2005-10-13 | 2008-07-30 | Glaxo Group Limited | Pyrrolopyrimidine derivatives as syk inhibitors |
| CA2651072A1 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| WO2009036066A1 (en) | 2007-09-10 | 2009-03-19 | Curis, Inc. | Vegfr inhibitors containing a zinc binding moiety |
| US9315449B2 (en) | 2008-05-15 | 2016-04-19 | Duke University | Substituted pyrazoles as heat shock transcription factor activators |
| WO2009143018A2 (en) | 2008-05-19 | 2009-11-26 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US20090325964A1 (en) | 2008-05-23 | 2009-12-31 | Wyeth | Piperazine Metabotropic Glutamate Receptor 5 (MGLUR5) Negative Allosteric Modulators For Anxiety/Depression |
| KR101705158B1 (ko) | 2009-05-05 | 2017-02-09 | 다나-파버 캔서 인스티튜트 인크. | Ｅｇｆｒ 억제제 및 질환 치료방법 |
| BR112012006859A2 (pt) | 2009-09-29 | 2019-09-24 | Glaxo Group Ltd | compostos |
| WO2011153553A2 (en) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| WO2012009258A2 (en) | 2010-07-13 | 2012-01-19 | Edward Roberts | Peptidomimetic galanin receptor modulators |
| WO2012045195A1 (en) | 2010-10-09 | 2012-04-12 | Abbott Laboratories | Pyrrolopyrimidines as fak and alk inhibiters for treatment of cancers and other diseases |
| CN103298474B (zh) | 2010-11-10 | 2016-06-29 | 无限药品股份有限公司 | 杂环化合物及其用途 |
| AU2011328139A1 (en) * | 2010-11-10 | 2013-04-04 | F. Hoffmann-La Roche Ag | Pyrazole aminopyrimidine derivatives as LRRK2 modulators |
| JP2014503528A (ja) | 2010-12-14 | 2014-02-13 | エレクトロプホレトイクス リミテッド | カゼインキナーゼ１δ（ＣＫ１δ）阻害剤及びタウオパチーなどの神経変性疾患の治療におけるその使用 |
| AU2012244550C1 (en) | 2011-04-21 | 2017-06-22 | Origenis Gmbh | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
| ES2575710T3 (es) * | 2011-09-22 | 2016-06-30 | Pfizer Inc | Derivados de pirrolopirimidina y purina |
| RU2650641C2 (ru) | 2011-11-30 | 2018-04-16 | Дженентек, Инк. | Фтор-18 и углерод-11 меченые радиолиганды для томографии с позитронной эмиссией (рет), визуализирующей lrrk2 |
| GB201204985D0 (en) | 2012-03-21 | 2012-05-02 | Genentech Inc | Compounds |
| BR112014027117B1 (pt) | 2012-05-03 | 2022-09-06 | Genentech, Inc | Derivados de pirazol aminopirimidina como moduladores de lrrk2, seus usos, e composição |
| CN106220615A (zh) | 2012-05-03 | 2016-12-14 | 霍夫曼-拉罗奇有限公司 | 作为lrrk2调节剂的吡唑氨基嘧啶衍生物 |
| EP3255049A1 (en) | 2012-06-29 | 2017-12-13 | Pfizer Inc | Novel 4-(substituted-amino)-7h-pyrrolo[2,3-d]pyrimidines as lrrk2 inhibitors |
| WO2015113451A1 (en) | 2014-01-29 | 2015-08-06 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
| UA118369C2 (uk) | 2014-01-29 | 2019-01-10 | Глаксосмітклайн Інтеллектьюел Проперті Девелопмент Лімітед | Сполуки, що інгібують активність lrrk2 кінази |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018155916A3 (ko) * | 2017-02-22 | 2018-12-06 | 재단법인 대구경북첨단의료산업진흥재단 | 피롤로-피리미딘 유도체 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| US11208412B2 (en) | 2017-02-22 | 2021-12-28 | Daegu-Gyeongbuk Medical Innovation Foundation | Pyrrolo-pyrimidine derivative compound, preparation method therefor, and pharmaceutical composition comprising same compound as effective ingredient for preventing or treating protein kinase-related disease |
| WO2020036437A1 (ko) * | 2018-08-16 | 2020-02-20 | 재단법인 대구경북첨단의료산업진흥재단 | 치환된 헤테로아릴 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
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