PL2364975T3 - Nowa pochodna amidu i jej zastosowanie jako lek - Google Patents
Nowa pochodna amidu i jej zastosowanie jako lekInfo
- Publication number
- PL2364975T3 PL2364975T3 PL09823571T PL09823571T PL2364975T3 PL 2364975 T3 PL2364975 T3 PL 2364975T3 PL 09823571 T PL09823571 T PL 09823571T PL 09823571 T PL09823571 T PL 09823571T PL 2364975 T3 PL2364975 T3 PL 2364975T3
- Authority
- PL
- Poland
- Prior art keywords
- medicine
- amide derivative
- novel amide
- novel
- derivative
- Prior art date
Links
- 150000001408 amides Chemical class 0.000 title 1
- 239000003814 drug Substances 0.000 title 1
Classifications
-
- 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
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008276147 | 2008-10-27 | ||
| EP09823571.6A EP2364975B1 (en) | 2008-10-27 | 2009-10-27 | Novel amide derivative and use thereof as medicine |
| PCT/JP2009/068386 WO2010050461A1 (ja) | 2008-10-27 | 2009-10-27 | 新規アミド誘導体およびその医薬としての用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL2364975T3 true PL2364975T3 (pl) | 2013-12-31 |
Family
ID=42128822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL09823571T PL2364975T3 (pl) | 2008-10-27 | 2009-10-27 | Nowa pochodna amidu i jej zastosowanie jako lek |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8354401B2 (pl) |
| EP (1) | EP2364975B1 (pl) |
| JP (1) | JP5478499B2 (pl) |
| KR (1) | KR101712679B1 (pl) |
| CN (1) | CN102239152B (pl) |
| AU (1) | AU2009310952B2 (pl) |
| CA (1) | CA2741661C (pl) |
| DK (1) | DK2364975T3 (pl) |
| ES (1) | ES2427397T3 (pl) |
| MX (1) | MX2011004372A (pl) |
| PL (1) | PL2364975T3 (pl) |
| PT (1) | PT2364975E (pl) |
| RU (1) | RU2487124C2 (pl) |
| TW (1) | TWI471322B (pl) |
| WO (1) | WO2010050461A1 (pl) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9051296B2 (en) | 2009-11-16 | 2015-06-09 | Raqualia Pharma Inc. | Aryl carboxamide derivatives as TTX-S blockers |
| JP2011246461A (ja) * | 2010-04-27 | 2011-12-08 | Mitsubishi Tanabe Pharma Corp | 新規アミド誘導体を含有する医薬組成物 |
| ES2653966T3 (es) * | 2010-04-27 | 2018-02-09 | Mitsubishi Tanabe Pharma Corporation | Nuevo derivado de amida y su uso como medicina |
| JP5800786B2 (ja) * | 2011-10-26 | 2015-10-28 | 田辺三菱製薬株式会社 | 新規アミド誘導体を有効成分として含有する医薬組成物 |
| WO2013134079A1 (en) | 2012-03-05 | 2013-09-12 | Amgen Inc. | Oxazolidinone compounds and derivatives thereof |
| AU2013353004A1 (en) | 2012-11-30 | 2015-07-09 | Kyowa Hakko Kirin Co., Ltd. | Nitrogen-containing heterocyclic compound |
| CN104262238B (zh) * | 2014-08-29 | 2016-08-03 | 西安交通大学 | 一种芳杂环联苯类Bcr-Abl抑制剂及其制备方法和应用 |
| US9556146B2 (en) | 2014-10-24 | 2017-01-31 | Biotherapeutics, Inc. | Lanthionine synthetase C-like 2-based therapeutics |
| US10407408B2 (en) * | 2015-07-09 | 2019-09-10 | Mitsubishi Tanabe Pharma Corporation | Imide derivatives and use thereof as medicine |
| JP6856555B2 (ja) * | 2017-01-06 | 2021-04-07 | 田辺三菱製薬株式会社 | 医薬組成物 |
| ES2970881T3 (es) * | 2018-11-14 | 2024-05-31 | Allinky Biopharma | Compuestos de piridin-sulfonamida para el tratamiento de afecciones relacionadas con interleucina 1 beta |
| WO2021127472A1 (en) | 2019-12-20 | 2021-06-24 | Landos Biopharma, Inc. | Lanthionine c-like protein 2 ligands, cells prepared therewith, and therapies using same |
| US12234578B2 (en) | 2020-01-29 | 2025-02-25 | Wisconsin Alumni Research Foundation | Tannin composite fibers |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK283420B6 (sk) * | 1992-05-08 | 2003-07-01 | Pharmacia & Upjohn Company | Antimikrobiálne oxazolidinóny obsahujúce substituované diazínové skupiny |
| JP2002513407A (ja) * | 1997-03-04 | 2002-05-08 | モンサント カンパニー | N−ヒドロキシ4−スルホニルブタンアミド化合物 |
| US6638952B1 (en) * | 1997-03-04 | 2003-10-28 | Pharmacia Corporation | Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds |
| US6750228B1 (en) * | 1997-11-14 | 2004-06-15 | Pharmacia Corporation | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
| JP2003535860A (ja) * | 2000-06-05 | 2003-12-02 | ドン・ア・ファーム・カンパニー・リミテッド | 新規なオキサゾリジノン誘導体及びその製造方法 |
| JP2003321368A (ja) * | 2002-04-30 | 2003-11-11 | Azwell Inc | N,n’−ジ置換ウレアまたはチオウレア化合物含有医薬 |
| JP4480128B2 (ja) | 2002-11-20 | 2010-06-16 | 独立行政法人科学技術振興機構 | マトリックスメタロプロテアーゼ−9の産生を阻害するための薬剤 |
| AU2003202753A1 (en) * | 2003-02-07 | 2004-08-30 | Ranbaxy Laboratories Limited | Oxazolidinone derivatives as antimicrobials |
| ZA200509147B (en) * | 2003-04-30 | 2007-03-28 | Morphochem Ag | Use of oxazolidinone-quinoline hybrid antibiotics for the treatment of anthrax and other infections |
| KR101101982B1 (ko) * | 2003-04-30 | 2012-01-02 | 모르포켐 악티엥게셀샤프트 퓌르 콤비나토리셰 케미 | 옥사졸리디논-퀴놀린 하이브리드 항생제의 탄저병 및 기타감염증의 치료용의 용도 |
| ATE401326T1 (de) | 2003-12-18 | 2008-08-15 | Morphochem Ag Komb Chemie | Oxazolidinon-chinolon hybrid antibiotika |
| CA2598457A1 (en) * | 2005-02-16 | 2006-08-24 | Schering Corporation | Pyridyl and phenyl substituted piperazine-piperidines with cxcr3 antagonist activity |
| JP5760248B2 (ja) | 2006-09-12 | 2015-08-05 | 国立大学法人東京農工大学 | 腫瘍の骨転移抑制および/または予防剤 |
| JP2008276147A (ja) | 2007-04-02 | 2008-11-13 | Seiko Epson Corp | 現像装置、画像形成装置、及び、画像形成システム |
-
2009
- 2009-10-27 RU RU2011121362/04A patent/RU2487124C2/ru active
- 2009-10-27 WO PCT/JP2009/068386 patent/WO2010050461A1/ja not_active Ceased
- 2009-10-27 CA CA2741661A patent/CA2741661C/en not_active Expired - Fee Related
- 2009-10-27 US US13/126,119 patent/US8354401B2/en not_active Expired - Fee Related
- 2009-10-27 JP JP2010535796A patent/JP5478499B2/ja not_active Expired - Fee Related
- 2009-10-27 MX MX2011004372A patent/MX2011004372A/es active IP Right Grant
- 2009-10-27 CN CN200980148589.7A patent/CN102239152B/zh not_active Expired - Fee Related
- 2009-10-27 PL PL09823571T patent/PL2364975T3/pl unknown
- 2009-10-27 KR KR1020117012045A patent/KR101712679B1/ko not_active Expired - Fee Related
- 2009-10-27 PT PT98235716T patent/PT2364975E/pt unknown
- 2009-10-27 DK DK09823571.6T patent/DK2364975T3/da active
- 2009-10-27 ES ES09823571T patent/ES2427397T3/es active Active
- 2009-10-27 TW TW98136276A patent/TWI471322B/zh not_active IP Right Cessation
- 2009-10-27 AU AU2009310952A patent/AU2009310952B2/en not_active Ceased
- 2009-10-27 EP EP09823571.6A patent/EP2364975B1/en not_active Not-in-force
Also Published As
| Publication number | Publication date |
|---|---|
| KR101712679B1 (ko) | 2017-03-22 |
| AU2009310952B2 (en) | 2015-04-30 |
| KR20110081312A (ko) | 2011-07-13 |
| MX2011004372A (es) | 2011-05-23 |
| ES2427397T3 (es) | 2013-10-30 |
| WO2010050461A1 (ja) | 2010-05-06 |
| TW201024290A (en) | 2010-07-01 |
| EP2364975A1 (en) | 2011-09-14 |
| CN102239152B (zh) | 2014-10-29 |
| PT2364975E (pt) | 2013-09-09 |
| US8354401B2 (en) | 2013-01-15 |
| AU2009310952A1 (en) | 2010-05-06 |
| EP2364975A4 (en) | 2012-05-02 |
| TWI471322B (zh) | 2015-02-01 |
| CA2741661A1 (en) | 2010-05-06 |
| CA2741661C (en) | 2016-12-13 |
| US20110263571A1 (en) | 2011-10-27 |
| JPWO2010050461A1 (ja) | 2012-03-29 |
| RU2487124C2 (ru) | 2013-07-10 |
| DK2364975T3 (da) | 2013-09-08 |
| JP5478499B2 (ja) | 2014-04-23 |
| CN102239152A (zh) | 2011-11-09 |
| RU2011121362A (ru) | 2012-12-10 |
| EP2364975B1 (en) | 2013-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PL2364975T3 (pl) | Nowa pochodna amidu i jej zastosowanie jako lek | |
| EP2150109A4 (en) | PHARMACEUTICAL USE OF SUBSTITUTED AMIDES | |
| IL209781A0 (en) | Novel immunoadjuvant flagellin-based compounds and use thereof | |
| IL212605A (en) | Pyrimidine-4-carboxamide cycles and their use as drugs | |
| GB0803018D0 (en) | Therapeutic compounds and their use | |
| IL211042A0 (en) | Imidazopyridin-2-one derivatives and uses thereof | |
| PL2307391T3 (pl) | Tiadiazolilooksyfenyloamidyny i ich zastosowanie jako środki grzybobójcze | |
| ZA201103635B (en) | Azaquinolinone derivatives and uses thereof | |
| ZA201007816B (en) | Novel substituted pyridin-2-ones and pyridazin-3-ones | |
| GB0817207D0 (en) | therapeutic apsac compounds and their use | |
| GB0804685D0 (en) | Therapeutic compounds and their use | |
| PL2307390T3 (pl) | Tiadiazolilooksyfenyloamidyny i ich zastosowanie jako środki grzybobójcze | |
| EP2336109A4 (en) | NOVEL PYRROLINONE DERIVATIVE AND DRUG COMPOSITION CONTAINING THE SAME | |
| GB0818241D0 (en) | Compounds and their use | |
| HUE037850T2 (hu) | Új amidszármazék és alkalmazása gyógyszerként | |
| GB0817208D0 (en) | Therapeutic apsap compounds and their use | |
| GB0807609D0 (en) | Therapeutic compounds and their use | |
| IL206594A (en) | The history of azinone-tetrahydropyridoindole and its containing pharmaceutical preparations | |
| EP2268281A4 (en) | THIENOPYRROLES AND PYRROLOTHIAZOLES AS NEW THERAPEUTIC AGENTS | |
| EP2412701A4 (en) | NEW AMIDE DERIVATIVE AND SKIN LAUNDERING AGENT | |
| IL215835A (en) | Carboxamide compounds and their use as a drug | |
| IL208771A0 (en) | Iminopyridine derivatives and use thereof | |
| PL2341047T3 (pl) | Pochodna cykloheksanowa i jej farmaceutyczne zastosowanie | |
| IL207423A0 (en) | Amide derivative and pharmaceutical composition containing the same | |
| GB0812913D0 (en) | Therapeutic compounds and their use |