KR102598466B1 - 인플루엔자 바이러스 복제의 억제제로서 유용한 피롤로피리미딘 유도체 - Google Patents
인플루엔자 바이러스 복제의 억제제로서 유용한 피롤로피리미딘 유도체 Download PDFInfo
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- KR102598466B1 KR102598466B1 KR1020197033668A KR20197033668A KR102598466B1 KR 102598466 B1 KR102598466 B1 KR 102598466B1 KR 1020197033668 A KR1020197033668 A KR 1020197033668A KR 20197033668 A KR20197033668 A KR 20197033668A KR 102598466 B1 KR102598466 B1 KR 102598466B1
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- 239000003112 inhibitor Substances 0.000 title claims description 19
- 241000712461 unidentified influenza virus Species 0.000 title abstract description 51
- 230000029812 viral genome replication Effects 0.000 title description 9
- 150000004944 pyrrolopyrimidines Chemical class 0.000 title 1
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- 125000001424 substituent group Chemical group 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
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- 108010006232 Neuraminidase Proteins 0.000 claims description 15
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
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- 239000004480 active ingredient Substances 0.000 claims description 10
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- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 150000001408 amides Chemical group 0.000 claims description 9
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 8
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- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 7
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- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical group C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 6
- 239000011574 phosphorus Substances 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004001 thioalkyl group Chemical group 0.000 claims description 5
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- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
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- NTOWWABYYWPKKJ-UHFFFAOYSA-N 3-bromo-5-chloro-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=C(Cl)C=C2C(Br)=C1 NTOWWABYYWPKKJ-UHFFFAOYSA-N 0.000 description 43
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 38
- JQBPIXJAJYUTKK-UHFFFAOYSA-N phenyl N-[2-(5-ethoxypentoxy)ethyl]carbamate Chemical compound C(C)OCCCCCOCCNC(OC1=CC=CC=C1)=O JQBPIXJAJYUTKK-UHFFFAOYSA-N 0.000 description 38
- 125000001072 heteroaryl group Chemical group 0.000 description 31
- 239000003795 chemical substances by application Substances 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
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- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 24
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- 125000004429 atom Chemical group 0.000 description 22
- JMDJTPCVJFJTSX-JFFVOTQRSA-N ethyl (2S,3S)-3-[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrrolo[2,3-d]pyrimidin-7-yl]bicyclo[2.2.2]octane-2-carboxylate Chemical compound ClC=1C=C2C(=NC=1)NC=C2C=1N=CC2=C(N=1)N(C=C2F)[C@@H]1[C@H](C2CCC1CC2)C(=O)OCC JMDJTPCVJFJTSX-JFFVOTQRSA-N 0.000 description 22
- 125000000623 heterocyclic group Chemical group 0.000 description 22
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Classifications
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- C07—ORGANIC CHEMISTRY
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- 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Otolaryngology (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762489167P | 2017-04-24 | 2017-04-24 | |
| US62/489,167 | 2017-04-24 | ||
| PCT/US2018/028986 WO2018200425A1 (en) | 2017-04-24 | 2018-04-24 | Pyrrolopyrimidine derivatives useful as inhibitors of influenza virus replication |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190140971A KR20190140971A (ko) | 2019-12-20 |
| KR102598466B1 true KR102598466B1 (ko) | 2023-11-03 |
Family
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| US (1) | US11014941B2 (https=) |
| EP (1) | EP3615545B1 (https=) |
| JP (1) | JP7165721B2 (https=) |
| KR (1) | KR102598466B1 (https=) |
| CN (1) | CN110637022B (https=) |
| AU (1) | AU2018257778B2 (https=) |
| CA (1) | CA3059449A1 (https=) |
| DK (1) | DK3615545T3 (https=) |
| EA (1) | EA039181B1 (https=) |
| ES (1) | ES2901875T3 (https=) |
| IL (1) | IL269900B (https=) |
| MX (1) | MX393113B (https=) |
| MY (1) | MY199746A (https=) |
| NZ (1) | NZ757442A (https=) |
| PH (1) | PH12019502376B1 (https=) |
| PL (1) | PL3615545T3 (https=) |
| SG (1) | SG11201909478UA (https=) |
| SM (1) | SMT202100684T1 (https=) |
| TW (1) | TWI778052B (https=) |
| WO (1) | WO2018200425A1 (https=) |
| ZA (1) | ZA201906327B (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2939148T3 (es) * | 2018-10-17 | 2023-04-19 | Cocrystal Pharma Inc | Combinaciones de inhibidores de la replicación del virus de la influenza |
| BR112021009254A2 (pt) * | 2018-11-13 | 2021-08-10 | Cocrystal Pharma, Inc. | formulações para produtos terapêuticos para influenza |
| KR102890026B1 (ko) * | 2019-04-26 | 2025-11-24 | 닛산 가가쿠 가부시키가이샤 | 아릴술폰산 에스테르 화합물의 제조 방법 |
| WO2022007966A1 (zh) * | 2020-07-10 | 2022-01-13 | 四川海思科制药有限公司 | Pb2抑制剂及其制备方法和用途 |
| WO2022109495A1 (en) * | 2020-11-23 | 2022-05-27 | The Regents Of The University Of California | Methods and compositions for linking rna stem loops |
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| WO2015073481A1 (en) | 2013-11-13 | 2015-05-21 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
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-
2018
- 2018-04-24 TW TW107113876A patent/TWI778052B/zh active
- 2018-04-24 JP JP2020507515A patent/JP7165721B2/ja active Active
- 2018-04-24 KR KR1020197033668A patent/KR102598466B1/ko active Active
- 2018-04-24 DK DK18723298.8T patent/DK3615545T3/da active
- 2018-04-24 PL PL18723298T patent/PL3615545T3/pl unknown
- 2018-04-24 PH PH1/2019/502376A patent/PH12019502376B1/en unknown
- 2018-04-24 US US16/603,951 patent/US11014941B2/en active Active
- 2018-04-24 SG SG11201909478U patent/SG11201909478UA/en unknown
- 2018-04-24 AU AU2018257778A patent/AU2018257778B2/en active Active
- 2018-04-24 CA CA3059449A patent/CA3059449A1/en active Pending
- 2018-04-24 CN CN201880030665.3A patent/CN110637022B/zh active Active
- 2018-04-24 SM SM20210684T patent/SMT202100684T1/it unknown
- 2018-04-24 NZ NZ757442A patent/NZ757442A/en unknown
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- 2018-04-24 MX MX2019012759A patent/MX393113B/es unknown
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- 2018-04-24 MY MYPI2019005805A patent/MY199746A/en unknown
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- 2018-04-24 WO PCT/US2018/028986 patent/WO2018200425A1/en not_active Ceased
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2019
- 2019-09-25 ZA ZA2019/06327A patent/ZA201906327B/en unknown
- 2019-10-07 IL IL269900A patent/IL269900B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010148197A1 (en) | 2009-06-17 | 2010-12-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| WO2015073481A1 (en) | 2013-11-13 | 2015-05-21 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
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| WO2018200425A1 (en) | 2018-11-01 |
| NZ757442A (en) | 2022-10-28 |
| US11014941B2 (en) | 2021-05-25 |
| PL3615545T3 (pl) | 2022-01-10 |
| ZA201906327B (en) | 2025-01-29 |
| EA201992543A1 (ru) | 2020-03-24 |
| AU2018257778B2 (en) | 2022-02-17 |
| JP7165721B2 (ja) | 2022-11-04 |
| TW201839003A (zh) | 2018-11-01 |
| PH12019502376B1 (en) | 2024-06-05 |
| CA3059449A1 (en) | 2018-11-01 |
| CN110637022A (zh) | 2019-12-31 |
| MX393113B (es) | 2025-03-24 |
| KR20190140971A (ko) | 2019-12-20 |
| SG11201909478UA (en) | 2019-11-28 |
| EP3615545A1 (en) | 2020-03-04 |
| BR112019022307A2 (pt) | 2020-05-26 |
| EA039181B1 (ru) | 2021-12-15 |
| MY199746A (en) | 2023-11-21 |
| US20200123177A1 (en) | 2020-04-23 |
| TWI778052B (zh) | 2022-09-21 |
| AU2018257778A1 (en) | 2019-10-10 |
| DK3615545T3 (da) | 2021-11-22 |
| EP3615545B1 (en) | 2021-09-01 |
| ES2901875T3 (es) | 2022-03-24 |
| SMT202100684T1 (it) | 2022-01-10 |
| CN110637022B (zh) | 2022-09-16 |
| MX2019012759A (es) | 2019-12-16 |
| PH12019502376A1 (en) | 2020-09-14 |
| IL269900B (en) | 2022-05-01 |
| JP2020517738A (ja) | 2020-06-18 |
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