ECSP19070413A - Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue - Google Patents
Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengueInfo
- Publication number
- ECSP19070413A ECSP19070413A ECSENADI201970413A ECDI201970413A ECSP19070413A EC SP19070413 A ECSP19070413 A EC SP19070413A EC SENADI201970413 A ECSENADI201970413 A EC SENADI201970413A EC DI201970413 A ECDI201970413 A EC DI201970413A EC SP19070413 A ECSP19070413 A EC SP19070413A
- Authority
- EC
- Ecuador
- Prior art keywords
- dengue viral
- inhibitors
- compounds
- indoline derivatives
- viral replication
- Prior art date
Links
Classifications
-
- 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
- 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
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- 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
-
- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
La presente invención se refiere a derivados de indolina sustituidos, a métodos para prevenir o tratar infecciones virales por dengue mediante el uso de dichos compuestos y también se refiere a dichos compuestos para su uso como medicamento, más preferentemente, para su uso como medicamento para tratar o prevenir infecciones virales por dengue. La presente invención se refiere además a composiciones farmacéuticas o preparados combinados de los compuestos, a las composiciones o preparados para su uso como un medicamento, más preferentemente para la prevención o el tratamiento de infecciones virales por dengue. La invención también se refiere a procesos para la preparación de los compuestos.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17164045 | 2017-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ECSP19070413A true ECSP19070413A (es) | 2019-10-31 |
Family
ID=58464339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ECSENADI201970413A ECSP19070413A (es) | 2017-03-31 | 2019-09-27 | Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US11179368B2 (es) |
| EP (1) | EP3601225B1 (es) |
| JP (1) | JP7038733B2 (es) |
| KR (1) | KR102556222B1 (es) |
| CN (1) | CN110612284B (es) |
| AR (1) | AR111315A1 (es) |
| AU (1) | AU2018246299A1 (es) |
| BR (1) | BR112019019928A2 (es) |
| CA (1) | CA3055260A1 (es) |
| CL (1) | CL2019002744A1 (es) |
| CO (1) | CO2019010292A2 (es) |
| CR (1) | CR20190447A (es) |
| DK (1) | DK3601225T3 (es) |
| EA (1) | EA201992334A1 (es) |
| EC (1) | ECSP19070413A (es) |
| ES (1) | ES2887673T3 (es) |
| HR (1) | HRP20211102T1 (es) |
| HU (1) | HUE055576T2 (es) |
| IL (1) | IL269657A (es) |
| JO (1) | JOP20180026A1 (es) |
| LT (1) | LT3601225T (es) |
| MA (1) | MA48987A (es) |
| MX (1) | MX2019011608A (es) |
| NI (1) | NI201900098A (es) |
| PE (1) | PE20191652A1 (es) |
| PH (1) | PH12019502095A1 (es) |
| SG (1) | SG11201908465QA (es) |
| SI (1) | SI3601225T1 (es) |
| TW (1) | TW201900610A (es) |
| UY (1) | UY37646A (es) |
| WO (1) | WO2018178238A1 (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
| 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 |
| CR20180496A (es) | 2016-03-31 | 2018-12-06 | Univ Leuven Kath | Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue |
| WO2017167950A1 (en) | 2016-03-31 | 2017-10-05 | Janssen Pharmaceuticals, Inc. | Substituted indole derivatives as dengue viral replication inhibitors |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CN109069482B (zh) | 2016-04-01 | 2022-04-05 | 杨森制药公司 | 作为登革热病毒复制抑制剂的经取代的吲哚化合物衍生物 |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| MX393586B (es) | 2017-05-22 | 2025-03-24 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue |
| PE20200342A1 (es) | 2017-05-22 | 2020-02-14 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue |
| CN109485596A (zh) * | 2018-12-19 | 2019-03-19 | 山东理工职业学院 | 一种含吲哚啉的登革病毒抑制剂的制备方法 |
| WO2025248536A1 (en) * | 2024-05-29 | 2025-12-04 | Zydus Lifesciences Limited | Novel oxime derivatives to treat viral infections |
| 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 |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1200899A (en) | 1997-10-27 | 1999-05-17 | Eli Lilly And Company | Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors |
| GB0110832D0 (en) | 2001-05-03 | 2001-06-27 | Virogen Ltd | Antiviral compounds |
| WO2003050295A2 (en) | 2001-12-12 | 2003-06-19 | 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 |
| AU2006204917A1 (en) | 2005-01-14 | 2006-07-20 | Smithkline Beecham Corporation | Indole derivatives for treating viral infections |
| EA200701669A1 (ru) | 2005-02-09 | 2008-02-28 | Мидженикс Инк. | Композиции и способы лечения или предотвращения инфекций, вызванных вирусами семейства flaviviridae |
| AP2010005480A0 (en) | 2008-06-03 | 2010-12-31 | Siga Technologies Inc | Small molecule inhibitors for the treatment or prevention of denque virus infection. |
| 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 |
| WO2010091413A1 (en) | 2009-02-09 | 2010-08-12 | Enanta Pharmaceuticals, Inc. | Linked 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 |
| US7948798B1 (en) | 2009-07-22 | 2011-05-24 | Marvell International Ltd. | Mixed multi-level cell and single level cell storage device |
| PT2523951E (pt) | 2010-01-15 | 2015-09-14 | Gilead Sciences Inc | Inibidores de vírus flaviviridae |
| 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 |
| 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 |
| KR102290189B1 (ko) | 2013-10-23 | 2021-08-17 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 카르복스아미드 유도체 및 b형 간염 치료용 의약으로서의 이의 용도 |
| TWI688564B (zh) | 2014-01-31 | 2020-03-21 | 美商必治妥美雅史谷比公司 | 作為凝血因子xia抑制劑之具有雜環p2'基團之巨環化合物 |
| PL3201177T3 (pl) | 2014-10-01 | 2019-05-31 | Janssen Pharmaceuticals Inc | Mono- lub di-podstawione indole jako inhibitory replikacji wirusa dengi |
| EP3201176B1 (en) | 2014-10-01 | 2018-12-12 | Janssen Pharmaceuticals, Inc. | Mono- or di-substituted indole derivatives as dengue viral replication inhibitors |
| NO2721243T3 (es) | 2014-10-01 | 2018-10-20 | ||
| 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 |
| 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 |
| EP3370698B1 (en) | 2015-11-03 | 2022-01-26 | Zoetis Services LLC | Sol-gel polymer composites and uses thereof |
| WO2017167950A1 (en) | 2016-03-31 | 2017-10-05 | Janssen Pharmaceuticals, Inc. | Substituted indole derivatives as dengue viral replication inhibitors |
| CR20180496A (es) | 2016-03-31 | 2018-12-06 | Univ Leuven Kath | Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue |
| EA036637B1 (ru) | 2016-03-31 | 2020-12-02 | Такеда Фармасьютикал Компани Лимитед | Гетероциклические спиросоединения, ингибирующие моноацилглицерин-липазу |
| CA3015934A1 (en) | 2016-04-01 | 2017-10-05 | Basf Se | Bicyclic compounds |
| BR112018070163A2 (pt) | 2016-04-01 | 2019-01-29 | Signal Pharm Llc | compostos de aminopurina substituída, composições e métodos de tratamento |
| PT3436079T (pt) | 2016-04-01 | 2021-10-06 | Kite Pharma Inc | Recetores de antigénios quiméricos e de células t e métodos de uso |
| CN109069482B (zh) | 2016-04-01 | 2022-04-05 | 杨森制药公司 | 作为登革热病毒复制抑制剂的经取代的吲哚化合物衍生物 |
| UA123276C2 (uk) | 2016-04-01 | 2021-03-10 | Кайт Фарма, Інк. | Химерний рецептор та спосіб лікування пухлини або злоякісного новоутворення |
| KR102694879B1 (ko) | 2016-04-01 | 2024-08-16 | 암젠 인크 | Flt3에 대한 키메라 수용체 및 이의 사용 방법 |
| 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 |
| PE20200342A1 (es) | 2017-05-22 | 2020-02-14 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue |
| MX393586B (es) | 2017-05-22 | 2025-03-24 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue |
-
2017
- 2017-03-31 JO JOP/2018/0026A patent/JOP20180026A1/ar unknown
-
2018
- 2018-03-28 AR ARP180100777A patent/AR111315A1/es unknown
- 2018-03-29 CA CA3055260A patent/CA3055260A1/en not_active Abandoned
- 2018-03-29 HR HRP20211102TT patent/HRP20211102T1/hr unknown
- 2018-03-29 PE PE2019001919A patent/PE20191652A1/es unknown
- 2018-03-29 DK DK18715611.2T patent/DK3601225T3/da active
- 2018-03-29 US US16/492,667 patent/US11179368B2/en active Active
- 2018-03-29 HU HUE18715611A patent/HUE055576T2/hu unknown
- 2018-03-29 EA EA201992334A patent/EA201992334A1/ru unknown
- 2018-03-29 SI SI201830334T patent/SI3601225T1/sl unknown
- 2018-03-29 MA MA048987A patent/MA48987A/fr unknown
- 2018-03-29 CN CN201880022012.0A patent/CN110612284B/zh active Active
- 2018-03-29 BR BR112019019928A patent/BR112019019928A2/pt not_active IP Right Cessation
- 2018-03-29 LT LTEPPCT/EP2018/058077T patent/LT3601225T/lt unknown
- 2018-03-29 MX MX2019011608A patent/MX2019011608A/es unknown
- 2018-03-29 ES ES18715611T patent/ES2887673T3/es active Active
- 2018-03-29 CR CR20190447A patent/CR20190447A/es unknown
- 2018-03-29 JP JP2019553485A patent/JP7038733B2/ja active Active
- 2018-03-29 AU AU2018246299A patent/AU2018246299A1/en not_active Abandoned
- 2018-03-29 EP EP18715611.2A patent/EP3601225B1/en active Active
- 2018-03-29 SG SG11201908465Q patent/SG11201908465QA/en unknown
- 2018-03-29 KR KR1020197031206A patent/KR102556222B1/ko active Active
- 2018-03-29 TW TW107110873A patent/TW201900610A/zh unknown
- 2018-03-29 WO PCT/EP2018/058077 patent/WO2018178238A1/en not_active Ceased
- 2018-04-02 UY UY0001037646A patent/UY37646A/es unknown
-
2019
- 2019-09-13 PH PH12019502095A patent/PH12019502095A1/en unknown
- 2019-09-24 CO CONC2019/0010292A patent/CO2019010292A2/es unknown
- 2019-09-25 IL IL26965719A patent/IL269657A/en unknown
- 2019-09-26 CL CL2019002744A patent/CL2019002744A1/es unknown
- 2019-09-27 NI NI201900098A patent/NI201900098A/es unknown
- 2019-09-27 EC ECSENADI201970413A patent/ECSP19070413A/es unknown
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