JP7434281B2 - Pad酵素のベンズイミダゾール阻害剤 - Google Patents
Pad酵素のベンズイミダゾール阻害剤 Download PDFInfo
- Publication number
- JP7434281B2 JP7434281B2 JP2021506660A JP2021506660A JP7434281B2 JP 7434281 B2 JP7434281 B2 JP 7434281B2 JP 2021506660 A JP2021506660 A JP 2021506660A JP 2021506660 A JP2021506660 A JP 2021506660A JP 7434281 B2 JP7434281 B2 JP 7434281B2
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- Prior art keywords
- substituted
- alkyl
- independently selected
- heterocyclyl
- aryl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/495—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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic 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
- A61K31/495—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862715845P | 2018-08-08 | 2018-08-08 | |
| US62/715,845 | 2018-08-08 | ||
| PCT/US2019/045459 WO2020033514A1 (en) | 2018-08-08 | 2019-08-07 | Benzimidazole inhibitors of pad enzymes |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021534104A JP2021534104A (ja) | 2021-12-09 |
| JP2021534104A5 JP2021534104A5 (https=) | 2022-08-16 |
| JPWO2020033514A5 JPWO2020033514A5 (https=) | 2022-08-16 |
| JP7434281B2 true JP7434281B2 (ja) | 2024-02-20 |
Family
ID=67766305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021506660A Active JP7434281B2 (ja) | 2018-08-08 | 2019-08-07 | Pad酵素のベンズイミダゾール阻害剤 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20220348562A1 (https=) |
| EP (1) | EP3833439B1 (https=) |
| JP (1) | JP7434281B2 (https=) |
| KR (1) | KR20210042933A (https=) |
| CN (1) | CN112789087B (https=) |
| ES (1) | ES2956090T3 (https=) |
| WO (1) | WO2020033514A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3833671B1 (en) | 2018-08-08 | 2022-08-24 | Bristol-Myers Squibb Company | Substituted thienopyrroles as pad4 inhibitors |
| AU2019319835A1 (en) | 2018-08-08 | 2021-03-25 | Bristol-Myers Squibb Company | Indole and azaindole inhibitors of PAD enzymes |
| EP4100405A1 (en) | 2020-02-06 | 2022-12-14 | Bristol-Myers Squibb Company | Macrocyclic pad4 inhibitors useful as immunosuppressant |
| TW202140477A (zh) | 2020-02-12 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 雜環pad4抑制劑 |
| EP4143189A1 (en) * | 2020-04-30 | 2023-03-08 | Gilead Sciences, Inc. | Macrocyclic inhibitors of peptidylarginine deiminases |
| TW202241884A (zh) | 2020-12-22 | 2022-11-01 | 美商基利科學股份有限公司 | 肽基精胺酸去亞胺酶之抑制劑 |
| WO2022140428A2 (en) | 2020-12-22 | 2022-06-30 | Gilead Sciences, Inc. | Inhibitors of peptidylarginine deiminases |
| WO2025024265A1 (en) | 2023-07-21 | 2025-01-30 | Bristol-Myers Squibb Company | Methods of assessing citrullination and activity of pad4 modulators |
| WO2026020127A2 (en) | 2024-07-19 | 2026-01-22 | Bristol-Myers Squibb Company | Methods of assessing citrullination and activity of pad2 modulators |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001021634A1 (en) | 1999-09-21 | 2001-03-29 | Lion Bioscience Ag | Benzimidazole derivatives and combinatorial libraries thereof |
| WO2010051245A1 (en) | 2008-11-03 | 2010-05-06 | Merck Sharp & Dohme Corp. | Benzimidazole and aza-benzimidazole carboxamides |
| JP2015522628A (ja) | 2012-07-26 | 2015-08-06 | グラクソ グループ リミテッドGlaxo Group L | Pad4阻害剤としての2−(アザインドール−2−イル)ベンズイミダゾール |
| WO2017100594A1 (en) | 2015-12-09 | 2017-06-15 | Padlock Therapeutics, Inc. | Bicyclic inhibitors of pad4 |
| WO2017147102A1 (en) | 2016-02-23 | 2017-08-31 | Padlock Therapeutics, Inc. | Heteroaryl inhibitors of pad4 |
| CN107311933A (zh) | 2017-06-28 | 2017-11-03 | 中国人民解放军军事医学科学院毒物药物研究所 | 一类苯并咪唑衍生物,及其制备方法和用途 |
| WO2018022897A1 (en) | 2016-07-27 | 2018-02-01 | Padlock Therapeutics, Inc. | Covalent inhibitors of pad4 |
| JP2018520105A (ja) | 2015-05-21 | 2018-07-26 | グラクソスミスクライン、インテレクチュアル、プロパテ | Pad4阻害剤としてのベンゾイミダゾール誘導体 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR107030A1 (es) * | 2015-12-09 | 2018-03-14 | Padlock Therapeutics Inc | Inhibidores aza-bencimidazol de pad4 |
-
2019
- 2019-08-07 CN CN201980064964.3A patent/CN112789087B/zh active Active
- 2019-08-07 US US17/265,840 patent/US20220348562A1/en active Pending
- 2019-08-07 ES ES19759140T patent/ES2956090T3/es active Active
- 2019-08-07 JP JP2021506660A patent/JP7434281B2/ja active Active
- 2019-08-07 WO PCT/US2019/045459 patent/WO2020033514A1/en not_active Ceased
- 2019-08-07 EP EP19759140.7A patent/EP3833439B1/en active Active
- 2019-08-07 KR KR1020217006470A patent/KR20210042933A/ko active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001021634A1 (en) | 1999-09-21 | 2001-03-29 | Lion Bioscience Ag | Benzimidazole derivatives and combinatorial libraries thereof |
| WO2010051245A1 (en) | 2008-11-03 | 2010-05-06 | Merck Sharp & Dohme Corp. | Benzimidazole and aza-benzimidazole carboxamides |
| JP2015522628A (ja) | 2012-07-26 | 2015-08-06 | グラクソ グループ リミテッドGlaxo Group L | Pad4阻害剤としての2−(アザインドール−2−イル)ベンズイミダゾール |
| JP2018520105A (ja) | 2015-05-21 | 2018-07-26 | グラクソスミスクライン、インテレクチュアル、プロパテ | Pad4阻害剤としてのベンゾイミダゾール誘導体 |
| WO2017100594A1 (en) | 2015-12-09 | 2017-06-15 | Padlock Therapeutics, Inc. | Bicyclic inhibitors of pad4 |
| WO2017147102A1 (en) | 2016-02-23 | 2017-08-31 | Padlock Therapeutics, Inc. | Heteroaryl inhibitors of pad4 |
| WO2018022897A1 (en) | 2016-07-27 | 2018-02-01 | Padlock Therapeutics, Inc. | Covalent inhibitors of pad4 |
| CN107311933A (zh) | 2017-06-28 | 2017-11-03 | 中国人民解放军军事医学科学院毒物药物研究所 | 一类苯并咪唑衍生物,及其制备方法和用途 |
Non-Patent Citations (2)
| Title |
|---|
| Future Medicinal Chemistry,2013年,5(15),pp.1-14 |
| Il Farmaco,1998年,53(6),pp.415-420 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20210042933A (ko) | 2021-04-20 |
| EP3833439B1 (en) | 2023-07-12 |
| ES2956090T3 (es) | 2023-12-13 |
| CN112789087A (zh) | 2021-05-11 |
| CN112789087B (zh) | 2024-08-13 |
| JP2021534104A (ja) | 2021-12-09 |
| WO2020033514A1 (en) | 2020-02-13 |
| US20220348562A1 (en) | 2022-11-03 |
| EP3833439A1 (en) | 2021-06-16 |
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