TW202035424A - 大環流感內切核酸酶抑制劑 - Google Patents
大環流感內切核酸酶抑制劑 Download PDFInfo
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- TW202035424A TW202035424A TW108136776A TW108136776A TW202035424A TW 202035424 A TW202035424 A TW 202035424A TW 108136776 A TW108136776 A TW 108136776A TW 108136776 A TW108136776 A TW 108136776A TW 202035424 A TW202035424 A TW 202035424A
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- Prior art keywords
- compound
- alkyl
- synthesis
- phenyl
- dione
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- 102000004533 Endonucleases Human genes 0.000 title description 3
- 108010042407 Endonucleases Proteins 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 757
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- 125000001424 substituent group Chemical group 0.000 claims description 85
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000005843 halogen group Chemical group 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- -1 -CH 2 -CH 2 -O- Chemical group 0.000 claims description 43
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000004043 oxo group Chemical group O=* 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical group 0.000 claims description 20
- 206010022000 influenza Diseases 0.000 claims description 20
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
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- 125000006430 alkyl cyclopropyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
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- 101150065749 Churc1 gene Proteins 0.000 claims description 10
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- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- YUCFVHQCAFKDQG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH] YUCFVHQCAFKDQG-UHFFFAOYSA-N 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000003566 oxetanyl group Chemical group 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 179
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- 238000005481 NMR spectroscopy Methods 0.000 description 167
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 166
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- 230000005526 G1 to G0 transition Effects 0.000 description 99
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- 239000012267 brine Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
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- 239000000706 filtrate Substances 0.000 description 23
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- ZRPFJAPZDXQHSM-UHFFFAOYSA-L 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole;dichloro-[(2-propan-2-yloxyphenyl)methylidene]ruthenium Chemical compound CC(C)OC1=CC=CC=C1C=[Ru](Cl)(Cl)=C1N(C=2C(=CC(C)=CC=2C)C)CCN1C1=C(C)C=C(C)C=C1C ZRPFJAPZDXQHSM-UHFFFAOYSA-L 0.000 description 12
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- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 6
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- 229950001577 trimetozine Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000005924 vaccine-induced immune response Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 1
- 229960001028 zanamivir Drugs 0.000 description 1
Classifications
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
-
- 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
- C07D471/22—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 systems contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862744060P | 2018-10-10 | 2018-10-10 | |
| US62/744,060 | 2018-10-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202035424A true TW202035424A (zh) | 2020-10-01 |
Family
ID=68242803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108136776A TW202035424A (zh) | 2018-10-10 | 2019-10-09 | 大環流感內切核酸酶抑制劑 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US11312727B1 (https=) |
| EP (1) | EP3864020A1 (https=) |
| JP (1) | JP2022512676A (https=) |
| KR (1) | KR20210074329A (https=) |
| CN (1) | CN113195502A (https=) |
| AU (1) | AU2019359539A1 (https=) |
| CA (1) | CA3115792A1 (https=) |
| MX (1) | MX2021004182A (https=) |
| TW (1) | TW202035424A (https=) |
| WO (1) | WO2020075080A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020197991A1 (en) | 2019-03-22 | 2020-10-01 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and their pharmaceutical use |
| WO2021191872A1 (en) * | 2020-03-26 | 2021-09-30 | Janssen Biopharma, Inc. | Heteroaryl-substituted macrocyclic flu endonuclease inhibitors |
| CN113444010B (zh) * | 2020-03-28 | 2023-09-05 | 南京正大天晴制药有限公司 | 一种沙芬酰胺有关物质的制备方法 |
| US12516070B2 (en) | 2020-05-21 | 2026-01-06 | Cisen Pharmaceutical Co., Ltd | Fused ring derivatives and use thereof in pharmacy |
| TW202146413A (zh) * | 2020-06-12 | 2021-12-16 | 大陸商上海翰森生物醫藥科技有限公司 | 含吡啶酮稠環類衍生物抑制劑、其製備方法和應用 |
| CA3192145A1 (en) | 2020-09-30 | 2022-04-07 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2022105669A1 (zh) * | 2020-11-17 | 2022-05-27 | 南京明德新药研发有限公司 | 含Se大环类化合物 |
| FI4196479T3 (fi) * | 2021-01-19 | 2024-01-17 | Gilead Sciences Inc | Substituoituja pyridotriatsiiniyhdisteitä ja niiden käyttöjä |
| EP4384178A4 (en) * | 2021-08-11 | 2025-07-02 | Merck Sharp & Dohme Llc | POLYCYCLIC CAP-DEPENDENT ENDONUCLEASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF INFLUENZA |
| CN118317964A (zh) * | 2021-11-17 | 2024-07-09 | 辰欣药业股份有限公司 | 一种稠环衍生物的晶型及其制备方法 |
| WO2025015300A2 (en) * | 2023-07-12 | 2025-01-16 | Apac Pharma, Llc | Hepoxilin analogs, methods, uses, and processes for preparation thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT2444400T (lt) * | 2009-06-15 | 2018-06-11 | Shionogi & Co., Ltd. | Pakeistasis policiklinis karbamoilpiridono darinys |
| MX2013003139A (es) * | 2010-09-24 | 2013-06-18 | Shionogi & Co | Profarmaco de derivado de carbamoilpiridona policiclica substituida. |
| ES2724581T3 (es) * | 2013-09-12 | 2019-09-12 | Janssen Biopharma Inc | Compuestos de piridazinona y usos de los mismos |
| JOP20170169A1 (ar) * | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
-
2019
- 2019-10-09 MX MX2021004182A patent/MX2021004182A/es unknown
- 2019-10-09 WO PCT/IB2019/058591 patent/WO2020075080A1/en not_active Ceased
- 2019-10-09 AU AU2019359539A patent/AU2019359539A1/en not_active Abandoned
- 2019-10-09 CA CA3115792A patent/CA3115792A1/en active Pending
- 2019-10-09 TW TW108136776A patent/TW202035424A/zh unknown
- 2019-10-09 EP EP19787467.0A patent/EP3864020A1/en not_active Withdrawn
- 2019-10-09 US US17/284,162 patent/US11312727B1/en active Active
- 2019-10-09 CN CN201980082149.XA patent/CN113195502A/zh active Pending
- 2019-10-09 KR KR1020217013939A patent/KR20210074329A/ko not_active Ceased
- 2019-10-09 JP JP2021519876A patent/JP2022512676A/ja not_active Withdrawn
-
2022
- 2022-03-15 US US17/694,757 patent/US20230002409A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA3115792A1 (en) | 2020-04-16 |
| US20230002409A1 (en) | 2023-01-05 |
| KR20210074329A (ko) | 2021-06-21 |
| MX2021004182A (es) | 2021-09-08 |
| CN113195502A (zh) | 2021-07-30 |
| EP3864020A1 (en) | 2021-08-18 |
| WO2020075080A1 (en) | 2020-04-16 |
| AU2019359539A1 (en) | 2021-04-29 |
| US11312727B1 (en) | 2022-04-26 |
| JP2022512676A (ja) | 2022-02-07 |
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