KR102359776B1 - 뎅기 바이러스 복제 억제제로서의 치환 인돌린 유도체 - Google Patents
뎅기 바이러스 복제 억제제로서의 치환 인돌린 유도체 Download PDFInfo
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- KR102359776B1 KR102359776B1 KR1020187028180A KR20187028180A KR102359776B1 KR 102359776 B1 KR102359776 B1 KR 102359776B1 KR 1020187028180 A KR1020187028180 A KR 1020187028180A KR 20187028180 A KR20187028180 A KR 20187028180A KR 102359776 B1 KR102359776 B1 KR 102359776B1
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- reduced pressure
- under reduced
- indolin
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- 241000725619 Dengue virus Species 0.000 title claims description 29
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 title abstract 2
- 230000029812 viral genome replication Effects 0.000 title description 3
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
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- 150000003839 salts Chemical class 0.000 claims description 23
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- 239000000969 carrier Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 239000012472 biological sample Substances 0.000 claims 4
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- 238000002360 preparation method Methods 0.000 abstract description 13
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
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- 238000000926 separation method Methods 0.000 description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
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- 150000003840 hydrochlorides Chemical class 0.000 description 17
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 125000001309 chloro group Chemical group Cl* 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- MCSWKSCZARDPJX-UHFFFAOYSA-N 5-methoxy-6-(trifluoromethyl)-2,3-dihydro-1h-indole Chemical compound C1=C(C(F)(F)F)C(OC)=CC2=C1NCC2 MCSWKSCZARDPJX-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- ZIMFCYSPYGTOTG-UHFFFAOYSA-N 2-(4-chloro-2-fluorophenyl)-1-[6-(trifluoromethoxy)-2,3-dihydroindol-1-yl]ethanone Chemical compound ClC1=CC(=C(C=C1)CC(=O)N1CCC2=CC=C(C=C12)OC(F)(F)F)F ZIMFCYSPYGTOTG-UHFFFAOYSA-N 0.000 description 5
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- BLRRJWAWRFPKLT-UHFFFAOYSA-N 4-methoxy-5-(trifluoromethoxy)-2-(2-trimethylsilylethynyl)aniline Chemical compound COC1=CC(=C(N)C=C1OC(F)(F)F)C#C[Si](C)(C)C BLRRJWAWRFPKLT-UHFFFAOYSA-N 0.000 description 5
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- KNMAZUXTEPXPOM-UHFFFAOYSA-N 5-methoxy-6-(trifluoromethyl)-1h-indole Chemical compound C1=C(C(F)(F)F)C(OC)=CC2=C1NC=C2 KNMAZUXTEPXPOM-UHFFFAOYSA-N 0.000 description 5
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- 239000000314 lubricant Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- 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)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16163488.6 | 2016-04-01 | ||
| EP16163488 | 2016-04-01 | ||
| PCT/EP2017/057661 WO2017167951A1 (en) | 2016-04-01 | 2017-03-31 | Substituted indoline derivatives as dengue viral replication inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20180132661A KR20180132661A (ko) | 2018-12-12 |
| KR102359776B1 true KR102359776B1 (ko) | 2022-02-07 |
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| KR1020187028180A Active KR102359776B1 (ko) | 2016-04-01 | 2017-03-31 | 뎅기 바이러스 복제 억제제로서의 치환 인돌린 유도체 |
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| EP (1) | EP3436437B1 (https=) |
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| CL (1) | CL2018002758A1 (https=) |
| CO (1) | CO2018009563A2 (https=) |
| CR (1) | CR20180493A (https=) |
| DK (1) | DK3436437T3 (https=) |
| EA (1) | EA037988B1 (https=) |
| EC (1) | ECSP18073293A (https=) |
| ES (1) | ES2884067T3 (https=) |
| HR (1) | HRP20211278T1 (https=) |
| HU (1) | HUE055577T2 (https=) |
| IL (1) | IL261948B (https=) |
| JO (1) | JOP20170069B1 (https=) |
| LT (1) | LT3436437T (https=) |
| MX (1) | MX381634B (https=) |
| MY (1) | MY195194A (https=) |
| PE (1) | PE20181778A1 (https=) |
| PH (1) | PH12018502077A1 (https=) |
| SG (1) | SG11201808409XA (https=) |
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| TW (1) | TWI723148B (https=) |
| UA (1) | UA125296C2 (https=) |
| UY (1) | UY37182A (https=) |
| WO (1) | WO2017167951A1 (https=) |
| ZA (1) | ZA201806482B (https=) |
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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 |
| 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 |
| 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 |
| BR112018069601A2 (pt) * | 2016-03-31 | 2019-01-29 | Janssen Pharmaceuticals Inc | derivados de indolina substituídos como inibidores da replicação viral da dengue |
| BR112018068676A2 (pt) | 2016-03-31 | 2019-01-15 | Janssen Pharmaceuticals Inc | derivados de indol substituídos como inibidores da replicação viral do 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 |
| 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 |
| CA3161338A1 (en) | 2019-11-15 | 2021-05-20 | Janssen Pharmaceuticals, Inc. | Treatment and prevention of dengue disease |
| WO2025248536A1 (en) * | 2024-05-29 | 2025-12-04 | Zydus Lifesciences Limited | Novel oxime derivatives to treat viral infections |
| 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 |
| 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 |
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| WO2013045516A1 (en) * | 2011-09-26 | 2013-04-04 | Katholieke Universiteit Leuven | Viral replication inhibitors |
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| 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 |
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| AU2017242539B2 (en) | 2016-04-01 | 2020-10-15 | Basf Se | Bicyclic compounds |
| 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 |
| 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 |
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2017
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2018
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- 2018-09-28 EC ECSENADI201873293A patent/ECSP18073293A/es unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2013045516A1 (en) * | 2011-09-26 | 2013-04-04 | Katholieke Universiteit Leuven | Viral replication inhibitors |
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