KR20160115933A - Irak4 억제제로서의 인다졸 화합물 - Google Patents
Irak4 억제제로서의 인다졸 화합물 Download PDFInfo
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- KR20160115933A KR20160115933A KR1020167021614A KR20167021614A KR20160115933A KR 20160115933 A KR20160115933 A KR 20160115933A KR 1020167021614 A KR1020167021614 A KR 1020167021614A KR 20167021614 A KR20167021614 A KR 20167021614A KR 20160115933 A KR20160115933 A KR 20160115933A
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- Prior art keywords
- indazol
- methyl
- mmol
- carboxamide
- oxazole
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Classifications
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- C07—ORGANIC CHEMISTRY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2025003987A1 (ko) * | 2023-06-29 | 2025-01-02 | 동화약품주식회사 | 신규한 카르복사마이드 유도체 화합물 및 이를 포함하는 약학적 조성물 |
| WO2026139915A1 (ko) * | 2024-12-26 | 2026-07-02 | 동화약품주식회사 | 신규한 카르복사마이드 유도체 화합물 및 이를 포함하는 약학적 조성물 |
Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| HK1231480A1 (zh) | 2014-01-10 | 2017-12-22 | Aurigene Discovery Technologies Limited | 作为irak4抑制剂的吲唑化合物 |
| IL311677B2 (en) | 2014-01-13 | 2025-06-01 | Aurigene Oncology Ltd | Bicyclic heterocyclyl derivatives as irak4 inhibitors |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| CA2952188A1 (en) * | 2014-06-20 | 2015-12-23 | Aurigene Discovery Technologies Limited | Substituted indazole compounds as irak4 inhibitors |
| JO3705B1 (ar) | 2014-11-26 | 2021-01-31 | Bayer Pharma AG | إندازولات مستبدلة جديدة، عمليات لتحضيرها، مستحضرات دوائية تحتوي عليها واستخدامها في إنتاج أدوية |
| EP3233840B1 (en) | 2014-12-16 | 2018-11-21 | Eudendron S.r.l. | Heterocyclic derivatives modulating activity of certain protein kinases |
| EP3195865A1 (de) | 2016-01-25 | 2017-07-26 | Bayer Pharma Aktiengesellschaft | Kombinationen von irak4 inhibitoren und btk inhibitoren |
| WO2016174183A1 (en) | 2015-04-30 | 2016-11-03 | Bayer Pharma Aktiengesellschaft | Combinations of inhibitors of irak4 with inhibitors of btk |
| CA2992406A1 (en) * | 2015-07-15 | 2017-01-19 | Aurigene Discovery Technologies Limited | Indazole and azaindazole compounds as irak-4 inhibitors |
| HK1256242A1 (zh) * | 2015-08-04 | 2019-09-20 | Rigel Pharmaceuticals, Inc. | 吲哚化合物以及制备和使用该化合物的方法 |
| ES2745284T3 (es) * | 2015-09-11 | 2020-02-28 | Boehringer Ingelheim Int | Heteroarilos sustituidos con pirazolilo y su uso como medicamentos |
| WO2017108744A1 (de) * | 2015-12-22 | 2017-06-29 | Bayer Pharma Aktiengesellschaft | Neue substituierte indazole, verfahren zu ihrer herstellung, pharmazeutische präparate die diese enthalten, sowie deren verwendung zur herstellung von arzneimitteln |
| US10435396B2 (en) | 2016-03-03 | 2019-10-08 | Bayer Pharma Aktiegesellschaft | 2-substituted indazoles, methods for producing same, pharmaceutical preparations that contain same, and use of same to produce drugs |
| CN109071491B (zh) | 2016-04-29 | 2020-08-21 | 拜耳医药股份有限公司 | 吲唑的合成 |
| SI3448848T1 (sl) | 2016-04-29 | 2024-01-31 | Bayer Pharma Aktiengesellschaft | Polimorfna oblika N-(6-(2-hidroksipropan-2-il)-2-(2-(metilsulfonil)etil)-2H-indazol-5-il) -6-(trifluormetil)piridin-2-karboksamida |
| WO2017207385A1 (de) | 2016-05-31 | 2017-12-07 | Bayer Pharma Aktiengesellschaft | Substituierte 3-methylindazole, verfahren zu ihrer herstellung, pharmazeutische präparate, die diese enthalten, sowie deren verwendung zur herstellung von arzneimitteln |
| SI3464266T1 (sl) * | 2016-06-01 | 2021-12-31 | Bayer Animal Health Gmbh | Substituirani indazoli, uporabni pri zdravljenju in preprečevanju alergijskih in/ali vnetnih bolezni pri živalih |
| WO2017207386A1 (de) | 2016-06-01 | 2017-12-07 | Bayer Pharma Aktiengesellschaft | Verwendung von 2-substituierten indazolen zur behandlung und prophylaxe von autoimmunerkrankungen |
| US11542261B2 (en) | 2016-08-17 | 2023-01-03 | Children's Hospital Medical Center | Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors |
| US11254667B2 (en) | 2016-08-17 | 2022-02-22 | Children's Hospital Medical Center | Substituted imidazo[1,2-A]pyridines as IRAK 1/4 and flt3 inhibitors |
| US10280164B2 (en) | 2016-09-09 | 2019-05-07 | Incyte Corporation | Pyrazolopyridone compounds and uses thereof |
| AR109596A1 (es) | 2016-09-09 | 2018-12-26 | Incyte Corp | Compuestos pirazolopiridina y sus usos |
| US20180072741A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyrimidine compounds and uses thereof |
| US20180072718A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyridine compounds and uses thereof |
| WO2018152220A1 (en) | 2017-02-15 | 2018-08-23 | Incyte Corporation | Pyrazolopyridine compounds and uses thereof |
| TW202340194A (zh) | 2017-02-16 | 2023-10-16 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒𠯤衍生物 |
| CN120267671A (zh) | 2017-03-31 | 2025-07-08 | 奥锐金肿瘤有限公司 | 用于治疗血液病的化合物和组合物 |
| US10722495B2 (en) | 2017-09-08 | 2020-07-28 | Incyte Corporation | Cyanoindazole compounds and uses thereof |
| MX2020003190A (es) | 2017-09-22 | 2020-11-11 | Kymera Therapeutics Inc | Degradadores de proteinas y usos de los mismos. |
| WO2019060693A1 (en) | 2017-09-22 | 2019-03-28 | Kymera Therapeutics, Inc. | CRBN LIGANDS AND USES THEREOF |
| US11174248B2 (en) | 2017-10-11 | 2021-11-16 | Merck Sharp & Dohme Corp. | Indazolyl-spiro[2.3]hexane-carbonitrile derivatives as LRRK2 inhibitors, pharmaceutical compositions, and uses thereof |
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| EP4410377A3 (en) | 2017-10-31 | 2024-11-13 | Curis, Inc. | Compounds and compositions for treating hematological disorders |
| US11065231B2 (en) | 2017-11-17 | 2021-07-20 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides |
| WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| EP3737666A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | PROTEIN DEGRADATION AGENTS AND ASSOCIATED USES |
| US11512080B2 (en) | 2018-01-12 | 2022-11-29 | Kymera Therapeutics, Inc. | CRBN ligands and uses thereof |
| CA3090275A1 (en) | 2018-02-14 | 2019-08-22 | Dana-Farber Cancer Institute, Inc. | Irak degraders and uses thereof |
| US10752635B2 (en) | 2018-02-20 | 2020-08-25 | Incyte Corporation | Indazole compounds and uses thereof |
| DK3755703T3 (da) | 2018-02-20 | 2022-06-27 | Incyte Corp | N-(phenyl)-2-(phenyl)pyrimidin-4-carboxamidderivater og relaterede forbindelser som hpk1-inhibitorer til behandling af kræft |
| US10745388B2 (en) | 2018-02-20 | 2020-08-18 | Incyte Corporation | Indazole compounds and uses thereof |
| US11299473B2 (en) | 2018-04-13 | 2022-04-12 | Incyte Corporation | Benzimidazole and indole compounds and uses thereof |
| US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
| US12454520B2 (en) | 2018-07-06 | 2025-10-28 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| TWI721483B (zh) | 2018-07-13 | 2021-03-11 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒𠯤衍生物 |
| US10899755B2 (en) | 2018-08-08 | 2021-01-26 | Incyte Corporation | Benzothiazole compounds and uses thereof |
| WO2020035019A1 (zh) * | 2018-08-17 | 2020-02-20 | 浙江海正药业股份有限公司 | 吲唑胺类衍生物及其制备方法和其在医药上的用途 |
| WO2020068729A1 (en) | 2018-09-25 | 2020-04-02 | Incyte Corporation | Pyrazolo[4,3-d]pyrimidine compounds as alk2 abd/or fgfr modulators |
| AU2019389174A1 (en) | 2018-11-30 | 2021-07-01 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| WO2020135513A1 (zh) * | 2018-12-25 | 2020-07-02 | 上海美悦生物科技发展有限公司 | 一种作为irak抑制剂的化合物 |
| GB201904375D0 (en) * | 2019-03-29 | 2019-05-15 | Galapagos Nv | Novel compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| WO2020259626A1 (zh) * | 2019-06-26 | 2020-12-30 | 南京明德新药研发有限公司 | 作为irak4抑制剂的咪唑并吡啶类化合物 |
| PH12022500002A1 (en) | 2019-06-28 | 2023-04-03 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| WO2021004533A1 (zh) * | 2019-07-10 | 2021-01-14 | 南京明德新药研发有限公司 | 作为irak4和btk多靶点抑制剂的噁唑类化合物 |
| US12558427B2 (en) | 2019-07-17 | 2026-02-24 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| KR20220059480A (ko) | 2019-08-06 | 2022-05-10 | 인사이트 코포레이션 | 고체 형태의 hpk1 억제제 |
| WO2021047677A1 (zh) * | 2019-09-12 | 2021-03-18 | 中国科学院上海药物研究所 | 一类irak4激酶抑制剂及其制备和应用 |
| JP7353474B2 (ja) * | 2019-09-24 | 2023-09-29 | 上海美悦生物科技発展有限公司 | Ｉｒａｋ阻害剤、その製造方法及び用途 |
| KR102782229B1 (ko) | 2019-10-02 | 2025-03-20 | (주)카이노스메드 | N-(1h-이미다졸-2-일)벤즈아미드 화합물 및 활성 성분으로 이를 포함하는 약학 조성물 |
| WO2021119159A1 (en) | 2019-12-10 | 2021-06-17 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| EP4076524A4 (en) | 2019-12-17 | 2023-11-29 | Kymera Therapeutics, Inc. | IRAQ DEGRADERS AND USES THEREOF |
| CA3161878A1 (en) | 2019-12-17 | 2021-06-24 | Matthew M. Weiss | Irak degraders and uses thereof |
| BR112022020020A2 (pt) | 2020-04-04 | 2022-11-22 | Pfizer | Métodos de tratamento da doença do coronavírus 2019 |
| TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
| EP4161521A4 (en) | 2020-06-03 | 2024-07-10 | Kymera Therapeutics, Inc. | DEUTERED IRAQ DEGRADERS AND USES THEREOF |
| US11866405B2 (en) | 2020-12-10 | 2024-01-09 | Astrazeneca Ab | Substituted indazoles as IRAK4 inhibitors |
| WO2022135338A1 (zh) * | 2020-12-25 | 2022-06-30 | 南京明德新药研发有限公司 | 酰胺噁唑类化合物 |
| AR124547A1 (es) | 2020-12-30 | 2023-04-05 | Kymera Therapeutics Inc | Degradadores de irak y sus usos |
| WO2022174268A1 (en) | 2021-02-15 | 2022-08-18 | Kymera Therapeutics, Inc. | Irak4 degraders and uses thereof |
| CA3214747A1 (en) | 2021-04-08 | 2022-10-13 | Reinhard Von Roemeling | Combination therapies for the treatment of cancer |
| CA3217792A1 (en) | 2021-05-07 | 2022-11-10 | Kymera Therapeutics, Inc | Cdk2 degraders and uses thereof |
| JP2024540080A (ja) | 2021-10-29 | 2024-10-31 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋ４分解剤およびその合成 |
| WO2023088435A1 (zh) * | 2021-11-19 | 2023-05-25 | 成都奥睿药业有限公司 | 三取代吡啶衍生物的制备及作为芳香烃受体调节物的应用 |
| CN117177965B (zh) * | 2021-12-23 | 2024-04-30 | 杭州多域生物技术有限公司 | 一种五元并六元化合物、制备方法、药物组合物和应用 |
| EP4472967A4 (en) | 2022-01-31 | 2026-04-15 | Kymera Therapeutics Inc | Iraqi Degradation Agents and Their Uses |
| ES3075943T3 (en) | 2022-03-23 | 2026-08-10 | Rigel Pharmaceuticals Inc | Pyrimid-2-yl-pyrazole compounds as irak inhibitors |
| CN115181066B (zh) * | 2022-06-14 | 2023-07-14 | 浙江宏元药业股份有限公司 | 一种6-氯-2-甲基-2h-吲唑-5-胺的合成方法 |
| EP4516787A4 (en) * | 2022-06-15 | 2025-12-24 | Hangzhou Polymed Biopharmaceuticals Inc | SIX-LINK COMPOUND FUSIONED TO A FIVE-LINK RING, RELATED PREPARATION PROCESS, AND ASSOCIATED PHARMACEUTICAL COMPOSITION AND USE |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1617840A4 (en) | 2003-05-01 | 2008-08-20 | Bristol Myers Squibb Co | PYRAZOLE AMID COMPOUNDS AS KINASE INHIBITORS |
| ATE556067T1 (de) | 2003-05-20 | 2012-05-15 | Ajinomoto Kk | Modulatoren des vanilloid rezeptors |
| US20050004133A1 (en) | 2003-06-05 | 2005-01-06 | Makings Lewis R. | Modulators of VR1 receptor |
| WO2005034870A2 (en) | 2003-10-07 | 2005-04-21 | Renovis, Inc. | Amide compounds and ion channel ligands and uses thereof |
| US7906533B2 (en) * | 2004-11-03 | 2011-03-15 | Bayer Schering Pharma Ag | Nicotinamide pyridinureas as vascular endothelial growth factor (VEGF) receptor kinase inhibitors |
| EP1655297A1 (en) * | 2004-11-03 | 2006-05-10 | Schering Aktiengesellschaft | Nicotinamide pyridinureas as vascular endothelial growth factor (VEGF) receptor kinase inhibitors |
| JP2008519850A (ja) | 2004-11-10 | 2008-06-12 | シンタ ファーマシューティカルズ コーポレーション | Ｉｌ−１２調節化合物 |
| CN102633783A (zh) | 2006-02-10 | 2012-08-15 | 转化技术制药公司 | 作为Aurora激酶抑制剂的苯并唑系衍生物、组合物和使用方法 |
| US8008481B2 (en) | 2006-03-31 | 2011-08-30 | Ericsson Anna M | Indazole compounds |
| CN101594909A (zh) * | 2006-09-07 | 2009-12-02 | 比奥根艾迪克Ma公司 | 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂 |
| NZ575410A (en) * | 2006-09-07 | 2012-03-30 | Biogen Idec Inc | 2-(1H-Indazol-3-ylamino)-1H-benzimidazole derivatives |
| EP2121621B1 (en) | 2006-12-08 | 2014-05-07 | Exelixis Patent Company LLC | Lxr and fxr modulators |
| WO2009011850A2 (en) * | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| JP5364875B2 (ja) | 2007-07-16 | 2013-12-11 | アッヴィ・インコーポレイテッド | タンパク質キナーゼ阻害薬としてのインダゾール類、ベンゾイソオキサゾール類およびベンゾイソチアゾール類 |
| US8399448B2 (en) | 2007-08-08 | 2013-03-19 | Merck Serono Sa | 6-amino-pyrimidine-4-carboxamide derivatives and related compounds which bind to the sphingosine 1-phosphate (S1P) receptor for the treatment of multiple sclerosis |
| EP2367598B1 (en) * | 2008-11-19 | 2014-04-09 | Merck Sharp & Dohme Corp. | Inhibitors of diacylglycerol acyltransferase |
| WO2010071819A1 (en) | 2008-12-19 | 2010-06-24 | Schering Corporation | Bicyclic heterocyclic derivatives and methods of use thereof |
| JP2012254939A (ja) | 2009-10-07 | 2012-12-27 | Astellas Pharma Inc | オキサゾール化合物 |
| US20130053382A1 (en) | 2010-04-30 | 2013-02-28 | Sunil Paliwal | Inhibitors of Phosphoinositide Dependent Kinase 1 (PDK1) |
| JP2011246389A (ja) * | 2010-05-26 | 2011-12-08 | Oncotherapy Science Ltd | Ｔｔｋ阻害作用を有する縮環ピラゾール誘導体 |
| JP5985473B2 (ja) | 2010-07-13 | 2016-09-06 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | ＩＲＡＫ４モジュレーターとしてのピラゾロ［１，５ａ］ピリミジン及びチエノ［３，２ｂ］ピリミジン誘導体 |
| HUE029617T2 (en) * | 2010-12-20 | 2017-03-28 | Merck Serono Sa | Indazolyl triazole derivatives as IRAK inhibitors |
| WO2013042137A1 (en) | 2011-09-19 | 2013-03-28 | Aurigene Discovery Technologies Limited | Bicyclic heterocycles as irak4 inhibitors |
| GB201119401D0 (en) | 2011-11-10 | 2011-12-21 | Ucb Pharma Sa | Therapeutic agents |
| WO2014003483A1 (en) * | 2012-06-29 | 2014-01-03 | Hanmi Pharm. Co., Ltd. | Fused pyrimidine derivatives having inhibitory activity on fms kinases |
| US9168257B2 (en) | 2013-05-22 | 2015-10-27 | Children's Hospital Medical Center | Combination therapy for MDS |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺，其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| HK1231480A1 (zh) | 2014-01-10 | 2017-12-22 | Aurigene Discovery Technologies Limited | 作为irak4抑制剂的吲唑化合物 |
| IL311677B2 (en) | 2014-01-13 | 2025-06-01 | Aurigene Oncology Ltd | Bicyclic heterocyclyl derivatives as irak4 inhibitors |
| JO3705B1 (ar) | 2014-11-26 | 2021-01-31 | Bayer Pharma AG | إندازولات مستبدلة جديدة، عمليات لتحضيرها، مستحضرات دوائية تحتوي عليها واستخدامها في إنتاج أدوية |
| HK1256242A1 (zh) | 2015-08-04 | 2019-09-20 | Rigel Pharmaceuticals, Inc. | 吲哚化合物以及制备和使用该化合物的方法 |
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2015
- 2015-01-07 HK HK17105242.6A patent/HK1231480A1/zh unknown
- 2015-01-07 CA CA2935880A patent/CA2935880A1/en not_active Abandoned
- 2015-01-07 US US15/110,309 patent/US10160753B2/en not_active Expired - Fee Related
- 2015-01-07 WO PCT/IB2015/050119 patent/WO2015104662A1/en not_active Ceased
- 2015-01-07 KR KR1020167021614A patent/KR20160115933A/ko not_active Withdrawn
- 2015-01-07 SG SG11201605408RA patent/SG11201605408RA/en unknown
- 2015-01-07 JP JP2016563277A patent/JP2017505337A/ja not_active Ceased
- 2015-01-07 EP EP15703102.2A patent/EP3092226B1/en not_active Revoked
- 2015-01-07 EA EA201691401A patent/EA201691401A1/ru unknown
- 2015-01-07 BR BR112016015983A patent/BR112016015983A2/pt not_active Application Discontinuation
- 2015-01-07 CN CN201580012991.8A patent/CN106458982A/zh active Pending
- 2015-01-07 AU AU2015205348A patent/AU2015205348A1/en not_active Abandoned
- 2015-01-07 MX MX2016009011A patent/MX2016009011A/es unknown
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2016
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- 2016-07-05 PH PH12016501338A patent/PH12016501338A1/en unknown
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2025003987A1 (ko) * | 2023-06-29 | 2025-01-02 | 동화약품주식회사 | 신규한 카르복사마이드 유도체 화합물 및 이를 포함하는 약학적 조성물 |
| WO2026139915A1 (ko) * | 2024-12-26 | 2026-07-02 | 동화약품주식회사 | 신규한 카르복사마이드 유도체 화합물 및 이를 포함하는 약학적 조성물 |
Also Published As
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| WO2015104662A1 (en) | 2015-07-16 |
| CA2935880A1 (en) | 2015-07-16 |
| JP2017505337A (ja) | 2017-02-16 |
| SG11201605408RA (en) | 2016-07-28 |
| CN106458982A (zh) | 2017-02-22 |
| US20160326151A1 (en) | 2016-11-10 |
| CU20160109A7 (es) | 2017-02-02 |
| HK1231480A1 (zh) | 2017-12-22 |
| US10160753B2 (en) | 2018-12-25 |
| BR112016015983A2 (pt) | 2017-08-08 |
| AU2015205348A1 (en) | 2016-07-28 |
| EP3092226A1 (en) | 2016-11-16 |
| EA201691401A1 (ru) | 2016-11-30 |
| PH12016501338A1 (en) | 2016-08-15 |
| MX2016009011A (es) | 2017-01-23 |
| IL246555A0 (en) | 2016-08-31 |
| EP3092226B1 (en) | 2019-03-13 |
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