KR102610493B1 - 뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 - Google Patents
뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 Download PDFInfo
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- KR102610493B1 KR102610493B1 KR1020217011966A KR20217011966A KR102610493B1 KR 102610493 B1 KR102610493 B1 KR 102610493B1 KR 1020217011966 A KR1020217011966 A KR 1020217011966A KR 20217011966 A KR20217011966 A KR 20217011966A KR 102610493 B1 KR102610493 B1 KR 102610493B1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- 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
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/08—Bridged systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
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| EP15166900 | 2015-05-08 | ||
| EP15166900.9 | 2015-05-08 | ||
| EP16163342 | 2016-03-31 | ||
| EP16163342.5 | 2016-03-31 | ||
| KR1020177031660A KR102610491B1 (ko) | 2015-05-08 | 2016-05-04 | 뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 |
| PCT/EP2016/059975 WO2016180696A1 (en) | 2015-05-08 | 2016-05-04 | Mono- or di-substituted indole derivatives as dengue viral replication inhibitors |
Related Parent Applications (1)
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| KR1020177031660A Division KR102610491B1 (ko) | 2015-05-08 | 2016-05-04 | 뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 |
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| KR20210048578A KR20210048578A (ko) | 2021-05-03 |
| KR102610493B1 true KR102610493B1 (ko) | 2023-12-05 |
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| KR1020217011966A Active KR102610493B1 (ko) | 2015-05-08 | 2016-05-04 | 뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 |
| KR1020177031660A Active KR102610491B1 (ko) | 2015-05-08 | 2016-05-04 | 뎅기 바이러스 복제 억제제로서의 １치환 또는 ２치환 인돌 유도체 |
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| GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
| GB201305376D0 (en) | 2013-03-25 | 2013-05-08 | Univ Leuven Kath | Novel viral replication inhibitors |
| ME03360B (me) * | 2014-10-01 | 2019-10-20 | Janssen Pharmaceuticals Inc | Mono- ili di-supsтituisani derivaтi indola као inhibiтori replikacije virusa denge |
| MX2017004298A (es) * | 2014-10-01 | 2017-07-19 | Janssen Pharmaceuticals Inc | Indoles mono o disustituidos como inhibidores de la replicacion del virus del denge. |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| BR112018068676A2 (pt) | 2016-03-31 | 2019-01-15 | Janssen Pharmaceuticals Inc | derivados de indol substituídos como inibidores da replicação viral do dengue |
| BR112018069601A2 (pt) | 2016-03-31 | 2019-01-29 | Janssen Pharmaceuticals Inc | derivados de indolina substituídos como inibidores da replicação viral da dengue |
| BR112018068956A2 (pt) | 2016-04-01 | 2019-01-22 | Janssen Pharmaceuticals Inc | derivados do composto indol substituídos como inibidores da replicação viral da dengue |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| EP3630723B1 (en) | 2017-05-22 | 2022-08-24 | Janssen Pharmaceuticals, Inc. | Substituted indoline derivatives as dengue viral replication inhibitors |
| UA125970C2 (uk) * | 2017-05-22 | 2022-07-20 | Янссен Фармасьютікалз, Інк. | Заміщені похідні індоліну як інгібітори реплікації вірусів денге |
| CA3161338A1 (en) | 2019-11-15 | 2021-05-20 | Janssen Pharmaceuticals, Inc. | Treatment and prevention of dengue disease |
| WO2022094816A1 (en) * | 2020-11-04 | 2022-05-12 | Janssen Pharmaceuticals, Inc. | Solid formulation |
| WO2022094817A1 (en) * | 2020-11-04 | 2022-05-12 | Janssen Pharmaceuticals, Inc. | Pharmaceutical formulation |
| CN113024440B (zh) * | 2021-03-17 | 2023-05-16 | 凯莱英医药集团（天津）股份有限公司 | 连续化合成取代吲哚-2-羧酸的方法 |
| CN117616010A (zh) * | 2021-06-29 | 2024-02-27 | 杨森制药公司 | 制备(s)-2-(4-氯-2-甲氧基苯基)-2-((3-甲氧基-5-(甲磺酰基)苯基)氨基)-1-(1h-吲哚-3-基)乙烯酮衍生物的方法 |
| WO2023218285A1 (en) | 2022-05-12 | 2023-11-16 | Janssen Pharmaceuticals, Inc. | Treatment or prevention of dengue viral infection |
| CN115521307B (zh) * | 2022-09-30 | 2023-09-22 | 甘肃皓天医药科技有限责任公司 | 一种5-卤代-7-氮杂吲哚的制备方法 |
| WO2025253267A1 (en) | 2024-06-06 | 2025-12-11 | Janssen Pharmaceuticals, Inc. | Combination of mosnodenvir and close analogs with nitd-688 for use in the treatment and prevention of dengue disease |
| WO2026018176A1 (en) | 2024-07-17 | 2026-01-22 | Janssen Pharmaceuticals, Inc. | 2-(4-chloro-2 methoxyphenyl)-2-((3-methoxy-5-(methylsulfonyl)phenyl)amino)-1-(5-(trifluoro¬methoxy)-1h-indol-3-yl)ethanone and pharmaceutical compositions comprising the same |
| WO2026057013A1 (zh) * | 2024-09-14 | 2026-03-19 | 华武生物医药技术(湖北)有限责任公司 | 一类登革热病毒复制抑制剂、其制备方法和用途 |
| CN119306651B (zh) * | 2024-10-11 | 2025-12-05 | 山东大学 | 一种吲哚3-酰胺类衍生物及其制备方法与应用 |
| CN121378100B (zh) * | 2025-12-24 | 2026-04-21 | 浙江大学医学院附属第二医院 | 一种苯并[g]吲哚衍生物及其在制备抗登革热药物中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013045516A1 (en) | 2011-09-26 | 2013-04-04 | Katholieke Universiteit Leuven | Viral replication inhibitors |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1039911B1 (en) | 1997-10-27 | 2005-05-25 | Eli Lilly And Company | MORPHOLINO-N-ETHYL ESTER PRODRUGS OF INDOLE sPLA 2 INHIBITORS |
| GB0110832D0 (en) | 2001-05-03 | 2001-06-27 | Virogen Ltd | Antiviral compounds |
| AU2002364566B2 (en) | 2001-12-12 | 2009-03-26 | Conforma Therapeutics Corporation | Assays and implements for determining and modulating HSP90 binding activity |
| GB0215293D0 (en) | 2002-07-03 | 2002-08-14 | Rega Foundation | Viral inhibitors |
| CN101103026A (zh) | 2005-01-14 | 2008-01-09 | 健亚生物科技公司 | 用于治疗病毒感染的吲哚衍生物 |
| KR20070102741A (ko) | 2005-02-09 | 2007-10-19 | 미게닉스 인코포레이티드 | 플라비비리대 감염증을 치료하거나 예방하기 위한 조성물및 방법 |
| FR2928645A1 (fr) * | 2008-03-14 | 2009-09-18 | Sanofi Aventis Sa | Nouveaux derives de carbazole inhibiteurs d'hsp90, compositions les contenant et utilisation |
| AP2010005480A0 (en) | 2008-06-03 | 2010-12-31 | Siga Technologies Inc | Small molecule inhibitors for the treatment or prevention of denque virus infection. |
| US20120040974A1 (en) * | 2008-08-18 | 2012-02-16 | Yale University | Mif modulators |
| US8143259B2 (en) | 2008-08-19 | 2012-03-27 | Janssen Pharmaceutica, Nv | Cold menthol receptor antagonists |
| TWI453207B (zh) | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶，其組合物及使用其之治療方法 |
| EP2393359A4 (en) | 2009-02-09 | 2012-10-03 | Enanta Pharm Inc | COMPOUND DIBENZIMIDAZOLE DERIVATIVES |
| GB0910003D0 (en) | 2009-06-11 | 2009-07-22 | Univ Leuven Kath | Novel compounds for the treatment of neurodegenerative diseases |
| US8993604B2 (en) | 2009-06-30 | 2015-03-31 | Siga Technologies, Inc. | Treatment and prevention of dengue virus infections |
| US8524764B2 (en) | 2010-01-15 | 2013-09-03 | Gilead Sciences, Inc. | Inhibitors of Flaviviridae viruses |
| JP2013523657A (ja) | 2010-03-26 | 2013-06-17 | グラクソ グループ リミテッド | キナーゼ阻害剤としてのインダゾリル‐ピリミジン |
| JP5716205B2 (ja) | 2011-03-29 | 2015-05-13 | 学校法人日本大学 | グルコシダーゼ活性阻害用組成物及びそのスクリーニング方法 |
| GB201305376D0 (en) | 2013-03-25 | 2013-05-08 | Univ Leuven Kath | Novel viral replication inhibitors |
| CA2923712C (en) | 2013-10-23 | 2021-11-02 | Janssen Sciences Ireland Uc | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| SG10201908467RA (en) | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| CN106459919B (zh) | 2014-06-04 | 2021-03-23 | 弗莱德哈钦森癌症研究中心 | 使用notch 1和/或notch 2激动剂扩增和植入干细胞 |
| AU2015269365A1 (en) | 2014-06-04 | 2016-12-15 | Amgen Inc. | Methods for harvesting mammalian cell cultures |
| NO2721243T3 (https=) | 2014-10-01 | 2018-10-20 | ||
| ME03360B (me) | 2014-10-01 | 2019-10-20 | Janssen Pharmaceuticals Inc | Mono- ili di-supsтituisani derivaтi indola као inhibiтori replikacije virusa denge |
| MX2017004298A (es) | 2014-10-01 | 2017-07-19 | Janssen Pharmaceuticals Inc | Indoles mono o disustituidos como inhibidores de la replicacion del virus del denge. |
| LT3957753T (lt) | 2014-10-10 | 2025-01-10 | Rutgers, The State University Of New Jersey | Polimerazės grandininės reakcijos pradmenys ir zondai, skirti mycobacterium tuberculosis |
| PH12017501272B1 (en) * | 2015-01-16 | 2023-01-11 | Janssen Pharmaceuticals Inc | Indole derivatives as dengue viral replication inhibitors |
| AR103680A1 (es) | 2015-02-23 | 2017-05-24 | Lilly Co Eli | Inhibidores selectivos de bace1 |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| ES2952726T3 (es) | 2015-07-22 | 2023-11-03 | Omeicos Therapeutics Gmbh | Análogos metabólicamente fuertes de CYP-eicosanoides para el tratamiento de enfermedad cardíaca |
| JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| RU2761212C2 (ru) | 2015-11-03 | 2021-12-06 | Зоэтис Сервисиз Ллс | Полимерные композиты, полученные по способу золь-гель, и их применение |
| EA036637B1 (ru) | 2016-03-31 | 2020-12-02 | Такеда Фармасьютикал Компани Лимитед | Гетероциклические спиросоединения, ингибирующие моноацилглицерин-липазу |
| BR112018068676A2 (pt) | 2016-03-31 | 2019-01-15 | Janssen Pharmaceuticals Inc | derivados de indol substituídos como inibidores da replicação viral do dengue |
| BR112018069601A2 (pt) | 2016-03-31 | 2019-01-29 | Janssen Pharmaceuticals Inc | derivados de indolina substituídos como inibidores da replicação viral da dengue |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CA3019650C (en) | 2016-04-01 | 2023-07-25 | Kite Pharma, Inc. | Chimeric receptors and methods of use thereof |
| AU2017242539B2 (en) | 2016-04-01 | 2020-10-15 | Basf Se | Bicyclic compounds |
| MX379513B (es) | 2016-04-01 | 2025-03-11 | Signal Pharm Llc | Compuestos de aminopurina sustituida, composiciones de estos y métodos de tratamiento con estos. |
| ES2891578T3 (es) | 2016-04-01 | 2022-01-28 | Kite Pharma Inc | Antígeno quimérico y receptores de células T y métodos de uso |
| BR112018068956A2 (pt) | 2016-04-01 | 2019-01-22 | Janssen Pharmaceuticals Inc | derivados do composto indol substituídos como inibidores da replicação viral da dengue |
| IL262061B2 (en) | 2016-04-01 | 2023-03-01 | Amgen Inc | Chimeric flt-3 receptors and methods of using them |
| JP6573745B2 (ja) | 2017-03-17 | 2019-09-11 | 三菱電機株式会社 | アダプティブアレーアンテナ装置 |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| UA125970C2 (uk) | 2017-05-22 | 2022-07-20 | Янссен Фармасьютікалз, Інк. | Заміщені похідні індоліну як інгібітори реплікації вірусів денге |
| EP3630723B1 (en) | 2017-05-22 | 2022-08-24 | Janssen Pharmaceuticals, Inc. | Substituted indoline derivatives as dengue viral replication inhibitors |
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2016
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- 2016-05-04 ES ES21159479T patent/ES2941674T3/es active Active
- 2016-05-04 CR CR20170490A patent/CR20170490A/es unknown
- 2016-05-04 US US15/571,930 patent/US10696632B2/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013045516A1 (en) | 2011-09-26 | 2013-04-04 | Katholieke Universiteit Leuven | Viral replication inhibitors |
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