KR20230167102A - 골수성 암 치료를 위한 lsd1 억제제의 조합물 - Google Patents
골수성 암 치료를 위한 lsd1 억제제의 조합물 Download PDFInfo
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- KR20230167102A KR20230167102A KR1020237038295A KR20237038295A KR20230167102A KR 20230167102 A KR20230167102 A KR 20230167102A KR 1020237038295 A KR1020237038295 A KR 1020237038295A KR 20237038295 A KR20237038295 A KR 20237038295A KR 20230167102 A KR20230167102 A KR 20230167102A
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- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- lsd1 inhibitor
- gilteritinib
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- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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Landscapes
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| EP21382676 | 2021-07-23 | ||
| PCT/EP2022/057386 WO2022214303A1 (en) | 2021-04-08 | 2022-03-21 | Combinations of lsd1 inhibitors for treating myeloid cancers |
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| AU2011244478B2 (en) | 2010-04-20 | 2014-07-17 | Fondazione IEO-CCM | Tranylcypromine derivatives as inhibitors of histone demethylase LSD1 and/or LSD2 |
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| EP2927212A4 (en) | 2012-11-28 | 2016-06-08 | Univ Kyoto | LSD1-SELECTIVE HEMMER WITH LYSINE STRUCTURE |
| EP2740474A1 (en) | 2012-12-05 | 2014-06-11 | Instituto Europeo di Oncologia S.r.l. | Cyclopropylamine derivatives useful as inhibitors of histone demethylases kdm1a |
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| WO2014164867A1 (en) | 2013-03-11 | 2014-10-09 | Imago Biosciences | Kdm1a inhibitors for the treatment of disease |
| US9918983B2 (en) | 2013-05-30 | 2018-03-20 | The Board Of Regents Of The Nevada System Of Higher Education On Behalf Of The University Of Nevada, Las Vegas | Suicidal LSD1 inhibitors targeting SOX2-expressing cancer cells |
| KR102288648B1 (ko) | 2013-06-19 | 2021-08-12 | 유니버시티 오브 유타 리서치 파운데이션 | 히스톤 데메틸라제 억제제로서의 치환된 (e)-n′-(1-페닐에틸리덴)벤조하이드라지드 동족체 |
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| AU2014306149B2 (en) | 2013-08-06 | 2019-09-19 | Imago Biosciences Inc. | KDM1A inhibitors for the treatment of disease |
| WO2015031564A2 (en) | 2013-08-30 | 2015-03-05 | University Of Utah | Substituted-1h-benzo[d]imidazole series compounds as lysine-specfic demethylase 1 (lsd1) inhibitors |
| PL3080100T3 (pl) | 2013-12-11 | 2023-03-06 | Celgene Quanticel Research, Inc. | Inhibitory lizyno-specyficznej demetylazy-1 |
| HRP20200662T1 (hr) * | 2014-02-04 | 2020-10-02 | Astellas Pharma Inc. | Ljekoviti pripravak koji sadrži spoj diamino heterocikličkog karboksamida kao aktivni sastojak |
| US10118903B2 (en) | 2014-02-07 | 2018-11-06 | Musc Foundation For Research Development | Aminotriazole-based KDM1A inhibitors as epigenetic modulators |
| KR102421235B1 (ko) | 2014-02-13 | 2022-07-15 | 인사이트 코포레이션 | Lsd1 저해제로서 사이클로프로필아민 |
| EP3392244A1 (en) | 2014-02-13 | 2018-10-24 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
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| US9527835B2 (en) | 2014-02-13 | 2016-12-27 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| JP2017508798A (ja) | 2014-03-07 | 2017-03-30 | ザ ジョンズ ホプキンス ユニバーシティ | ヒストンリジン特異的デメチラーゼ（ｌｓｄ１）およびヒストンデアセチラーゼ（ｈｄａｃ）の阻害剤 |
| HUE057895T2 (hu) | 2014-05-01 | 2022-06-28 | Celgene Quanticel Res Inc | Lizinspecifikus demetiláz-1 inhibitorai |
| AU2015265820C1 (en) | 2014-05-30 | 2020-01-16 | Ieo - Istituto Europeo Di Oncologia S.R.L. | Cyclopropylamine compounds as histone demethylase inhibitors |
| CN104119280B (zh) | 2014-06-27 | 2016-03-16 | 郑州大学 | 含氨基类脲与端炔结构单元的嘧啶衍生物、制备方法及应用 |
| MX376632B (es) | 2014-06-27 | 2025-03-07 | Celgene Quanticel Res Inc | Inhibidores de demetilasa-1 especifica de lisina. |
| EA033698B1 (ru) | 2014-07-03 | 2019-11-18 | Celgene Quanticel Res Inc | Ингибиторы лизинспецифической деметилазы-1 |
| MX391865B (es) | 2014-07-03 | 2025-03-21 | Celgene Quanticel Res Inc | Inhibidores de demetilasa-1 especifica de lisina. |
| WO2016007731A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Imidazopyridines and imidazopyrazines as lsd1 inhibitors |
| WO2016007722A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| US9758523B2 (en) | 2014-07-10 | 2017-09-12 | Incyte Corporation | Triazolopyridines and triazolopyrazines as LSD1 inhibitors |
| US9695180B2 (en) | 2014-07-10 | 2017-07-04 | Incyte Corporation | Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors |
| EP2993175A1 (en) | 2014-09-05 | 2016-03-09 | IEO - Istituto Europeo di Oncologia Srl | Thienopyrroles as histone demethylase inhibitors |
| ES2935114T3 (es) | 2014-09-05 | 2023-03-01 | Celgene Quanticel Res Inc | Inhibidores de la desmetilasa 1 específica de lisina |
| WO2016123387A1 (en) | 2015-01-30 | 2016-08-04 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| KR102626978B1 (ko) | 2015-02-12 | 2024-01-18 | 이마고 바이오사이언시즈 인코포레이티드 | 질환 치료를 위한 kdm1a 저해제 |
| CN106146361A (zh) | 2015-03-16 | 2016-11-23 | 四川大学 | 茚-1-亚基磺酰基苯甲酰肼衍生物及其制备方法和用途 |
| UA122688C2 (uk) | 2015-04-03 | 2020-12-28 | Інсайт Корпорейшн | Гетероциклічні сполуки як інгібітори lsd1 |
| CN106045862B (zh) | 2015-04-10 | 2019-04-23 | 上海迪诺医药科技有限公司 | 环丙胺类螺(杂)环化合物、其药物组合物及应用 |
| US10526287B2 (en) | 2015-04-23 | 2020-01-07 | Constellation Pharmaceuticals, Inc. | LSD1 inhibitors and uses thereof |
| EP3090998A1 (en) | 2015-05-06 | 2016-11-09 | F. Hoffmann-La Roche AG | Solid forms |
| US20170001970A1 (en) | 2015-07-02 | 2017-01-05 | University Of Utah Research Foundation | Substituted benzohydrazide analogs as histone demethylase inhibitors |
| JP7427363B2 (ja) | 2015-08-12 | 2024-02-05 | インサイト・ホールディングス・コーポレイション | Ｌｓｄ１阻害剤の塩 |
| RS61404B1 (sr) | 2015-11-05 | 2021-02-26 | Celgene Quanticel Research Inc | Kompozicije koje sadrže inhibitor lizin specifične demetilaze-1 koje imaju pirimidinski prsten i njihova primena u lečenju kancera |
| US10059668B2 (en) | 2015-11-05 | 2018-08-28 | Mirati Therapeutics, Inc. | LSD1 inhibitors |
| CA3006434C (en) | 2015-11-27 | 2021-03-16 | Taiho Pharmaceutical Co., Ltd. | Biphenyl compound or salt thereof |
| WO2017109061A1 (en) | 2015-12-23 | 2017-06-29 | Ieo - Istituto Europeo Di Oncologia S.R.L. | Spirocyclopropylamine derivatives useful as inhibitors of histone demethylases kdm1a |
| CN105541806A (zh) | 2015-12-25 | 2016-05-04 | 中国药科大学 | 巴比妥酸类化合物、制备方法及其应用 |
| SG11201805645QA (en) | 2015-12-29 | 2018-07-30 | Mirati Therapeutics Inc | Lsd1 inhibitors |
| CN105924362B (zh) | 2016-02-05 | 2018-08-17 | 上海龙翔生物医药开发有限公司 | 芳香环丙基胺类化合物、其药学上可接受的盐、其制备方法及其用途 |
| CN110267945A (zh) | 2016-03-01 | 2019-09-20 | 诺华股份有限公司 | 氰基取代的吲哚化合物及其作为lsd1抑制剂的用途 |
| CN107176927B (zh) | 2016-03-12 | 2020-02-18 | 福建金乐医药科技有限公司 | 组蛋白去甲基化酶lsd1抑制剂 |
| CN107174584B (zh) | 2016-03-12 | 2020-09-01 | 福建金乐医药科技有限公司 | 含哌嗪结构化合物在制备lsd1抑制剂中的应用 |
| US11013698B2 (en) * | 2016-03-15 | 2021-05-25 | Oryzon Genomics S.A. | Combinations of LSD1 inhibitors for the treatment of hematological malignancies |
| CN107200706A (zh) | 2016-03-16 | 2017-09-26 | 中国科学院上海药物研究所 | 一类氟取代的环丙胺类化合物及其制备方法、药物组合物和用途 |
| US20170283397A1 (en) | 2016-03-31 | 2017-10-05 | University Of Utah Research Foundation | Substituted 1-h-indol-3-yl-benzamide and 1, 1'-biphenyl analogs as histone demethylase inhibitors |
| US10166221B2 (en) | 2016-04-22 | 2019-01-01 | Incyte Corporation | Formulations of an LSD1 inhibitor |
| SI3455204T1 (sl) | 2016-05-09 | 2026-03-31 | Jubilant Epicore LLC | Ciklopropil-amidne spojine kot dvojni zaviralci lsd1/hdac |
| EP3246330A1 (en) | 2016-05-18 | 2017-11-22 | Istituto Europeo di Oncologia S.r.l. | Imidazoles as histone demethylase inhibitors |
| CN106045881B (zh) | 2016-05-26 | 2017-10-31 | 新乡医学院 | 一类白藜芦醇衍生物、其制备方法及作为lsd1抑制剂的应用 |
| CN107459476B (zh) | 2016-06-03 | 2022-06-24 | 中国科学院上海药物研究所 | 反吲哚啉环丙胺类化合物及其制备方法、药物组合物和用途 |
| CN107513068A (zh) | 2016-06-16 | 2017-12-26 | 中国科学院上海药物研究所 | 一种具有fgfr抑制活性的新型化合物及其制备和应用 |
| US11390590B2 (en) | 2016-08-16 | 2022-07-19 | Imago Biosciences, Inc. | Methods and processes for the preparation of KDM1A inhibitors |
| CN106478639B (zh) | 2016-09-05 | 2018-09-18 | 郑州大学 | 嘧啶并1,2,4–三氮唑类的lsd1抑制剂、其制备方法及应用 |
| CN106432248B (zh) | 2016-09-27 | 2018-11-27 | 郑州大学 | 含嘧啶并三氮唑类lsd1抑制剂、其制备方法及应用 |
| MD3532459T2 (ro) | 2016-10-26 | 2024-06-30 | Constellation Pharmaceuticals Inc | Inhibitori ai LSD1 și utilizările medicale ale acestora |
| WO2018081342A1 (en) | 2016-10-26 | 2018-05-03 | Constellation Pharmaceuticals, Inc. | Lsd1 inhibitors and uses thereof |
| JP7217712B2 (ja) | 2017-01-24 | 2023-02-03 | シーエスピーシー ジョォンチィ ファーマシューティカル テクノロジー （シージアジョァン）カンパニー，リミテッド | Ｌｓｄ１阻害剤、その製造方法及び応用 |
| CN108530302A (zh) | 2017-03-06 | 2018-09-14 | 华东师范大学 | 2`,3`-二氢螺[环丙烷-1,1`-茚]-2-胺衍生物及其制备方法和应用 |
| CN106831489B (zh) | 2017-03-23 | 2018-04-17 | 郑州大学 | 苯环丙胺酰腙类化合物、制备方法及其应用 |
| CN106928235A (zh) | 2017-05-03 | 2017-07-07 | 郑州大学 | 含嘧啶并三氮唑类lsd1抑制剂、其制备方法及应用 |
| CN107033148B (zh) | 2017-05-03 | 2018-10-26 | 郑州大学 | 含嘧啶并三氮唑—巯基四氮唑类lsd1抑制剂、其制备方法及应用 |
| AU2018269947B2 (en) | 2017-05-15 | 2021-10-14 | The Regents Of The University Of Michigan | Pyrrolo(2,3-c)pyridines and related analogs as LSD-1 inhibitors |
| CN110740991B (zh) | 2017-05-26 | 2023-07-04 | 大鹏药品工业株式会社 | 新型联苯化合物或其盐 |
| KR20180134675A (ko) | 2017-06-09 | 2018-12-19 | 한미약품 주식회사 | 시클로프로필아민 유도체 화합물 및 이의 용도 |
| UY37774A (es) | 2017-06-19 | 2019-01-31 | Novartis Ag | Compuestos 5-cianoindol sustituidos y usos de los mismos |
| JP2020152641A (ja) | 2017-07-07 | 2020-09-24 | 国立研究開発法人理化学研究所 | リジン特異的脱メチル化酵素１阻害活性を有する新規化合物、その製造方法及びその用途 |
| ES2986559T3 (es) | 2017-08-18 | 2024-11-11 | St Europeo Di Oncologia S R L | Derivados de indol como inhibidores de la histona desmetilasa |
| CN107474011B (zh) | 2017-08-25 | 2020-03-27 | 新乡医学院 | 一类2-苯基-4-苯乙烯基吡啶类lsd1抑制剂、其制备方法及应用 |
| CN107501169B (zh) | 2017-08-25 | 2020-03-27 | 新乡医学院 | 一类反式二芳基乙烯类lsd1抑制剂、其制备方法及应用 |
| AR112900A1 (es) | 2017-09-13 | 2019-12-26 | Hanmi Pharm Ind Co Ltd | Compuesto derivado de pirazol y uso de este |
| CN109535019B (zh) | 2017-09-21 | 2021-08-20 | 华东师范大学 | 1,1a,6,6a-四氢环丙并[a]茚-1-胺衍生物及其制备方法与应用 |
| KR20190040783A (ko) | 2017-10-11 | 2019-04-19 | 한미약품 주식회사 | 라이신 특이적 데메틸라제-1 억제제로서의 피라졸 유도체 |
| KR20190040763A (ko) | 2017-10-11 | 2019-04-19 | 한미약품 주식회사 | 피라졸로피리딘 유도체 화합물 및 이의 용도 |
| CN107936022A (zh) | 2017-11-30 | 2018-04-20 | 郑州大学 | 黄嘌呤类lsd1抑制剂及其制备方法和应用 |
| CN110204551B (zh) | 2018-02-28 | 2021-08-17 | 中国科学院上海药物研究所 | 一类含环丙胺结构的噻吩并[3,2-d]嘧啶衍生物、其制备方法与用途 |
| US20210228490A1 (en) | 2018-05-04 | 2021-07-29 | Oryzon Genomics, S.A. | Stable pharmaceutical formulation |
| KR102684364B1 (ko) | 2018-05-11 | 2024-07-11 | 이마고 바이오사이언시즈 인코포레이티드 | 질환의 치료를 위한 kdm1a 저해제 |
| US11944614B2 (en) | 2018-05-15 | 2024-04-02 | Regents Of The University Of Michigan | Imidazo[4,5-c]pyridine compounds as LSD-1 inhibitors |
| WO2020015745A1 (zh) | 2018-07-20 | 2020-01-23 | 南京明德新药研发有限公司 | 一种lsd1抑制剂的盐及其晶型 |
| WO2020047198A1 (en) | 2018-08-31 | 2020-03-05 | Incyte Corporation | Salts of an lsd1 inhibitor and processes for preparing the same |
| CN112672994B (zh) | 2018-09-13 | 2022-09-13 | 南昌弘益药业有限公司 | 作为lsd1抑制剂的杂螺环类化合物及其应用 |
| US11649245B2 (en) | 2018-09-13 | 2023-05-16 | Helioeast Pharmaceutical Co., Ltd. | Cyclopropylamine compound as LSD1 inhibitor and use thereof |
| CN109265462B (zh) | 2018-10-31 | 2020-06-02 | 郑州大学 | 嘧啶并1,2,4-三氮唑类化合物及其制备方法和应用 |
| CN109293664B (zh) | 2018-11-14 | 2020-06-02 | 郑州大学 | 嘧啶并1,2,4-三氮唑肼类化合物及其制备方法和应用 |
| JPWO2020138398A1 (ja) | 2018-12-28 | 2021-11-04 | 国立研究開発法人理化学研究所 | リジン特異的脱メチル化酵素１を阻害する新規化合物、その製造方法及びその用途 |
| EP3907225A4 (en) | 2019-02-01 | 2022-09-14 | Hanmi Pharm. Co., Ltd. | COMPOUNDS DERIVED FROM IMIDAZOPYRIDINE AND THEIR USE |
| WO2020159285A1 (ko) | 2019-02-01 | 2020-08-06 | 한미약품 주식회사 | 이미다조피리딘 유도체 화합물 및 이의 용도 |
| CN112110936B (zh) | 2019-06-20 | 2021-12-07 | 沈阳药科大学 | 四氢喹啉类衍生物及其制备方法和应用 |
| CN110478352A (zh) | 2019-08-30 | 2019-11-22 | 郑州大学 | 含三唑基的5-氰基-6-苯基-嘧啶类化合物在抑制lsd1中的应用及lsd1抑制剂 |
| WO2021058024A1 (zh) | 2019-09-29 | 2021-04-01 | 南京明德新药研发有限公司 | Lsd1抑制剂 |
| WO2021095840A1 (en) | 2019-11-13 | 2021-05-20 | Taiho Pharmaceutical Co., Ltd. | METHODS OF TREATING LSD1-RELATED DISEASES and Disorders WITH LSD1 INHIBITORS |
| CN111072610B (zh) | 2019-12-16 | 2022-08-30 | 杭州师范大学 | 一类取代的苯并呋喃2-甲酰腙类lsd1抑制剂的制备和应用 |
| CN113354622B (zh) | 2020-03-06 | 2022-11-01 | 沈阳药科大学 | 对苯二胺类lsd1抑制剂及其制备方法 |
| CN111454252B (zh) | 2020-05-13 | 2021-06-11 | 郑州大学 | 含芳环/芳杂环-三氮唑-亚甲基-tcp衍生物及其制备方法和应用 |
| CN114105950B (zh) | 2020-08-31 | 2022-09-06 | 南京明德新药研发有限公司 | 吡唑类化合物及其应用 |
| CN112409310B (zh) | 2020-12-18 | 2023-04-21 | 许昌学院 | 一种具有lsd1抑制活性的化合物、制备方法及应用 |
| CN113087712B (zh) | 2021-04-12 | 2022-02-22 | 郑州大学 | L-氨基酸-6-胶霉毒素酯三氟乙酸盐及其制备方法 |
| CN113105479B (zh) | 2021-04-12 | 2022-07-01 | 郑州大学 | 胶霉毒素6-芳香环羧酸酯系列衍生物及其制备方法 |
| CN113264903A (zh) | 2021-05-27 | 2021-08-17 | 郑州大学 | 一种吩噻嗪类化合物及其制备方法和应用 |
| CN113599380A (zh) | 2021-08-24 | 2021-11-05 | 郑州大学 | 小檗碱类化合物在制备抗肿瘤药物中的应用 |
| CN113582906B (zh) | 2021-08-24 | 2023-05-16 | 郑州大学 | 二氟苯环丙胺类化合物及其制备方法和应用 |
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| BR112023020554A2 (pt) | 2023-12-05 |
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