CY1107383T1 - Αναστολεις της φωσφολιπασης α2 του κυτοπλασμικου διαλυματος - Google Patents
Αναστολεις της φωσφολιπασης α2 του κυτοπλασμικου διαλυματοςInfo
- Publication number
- CY1107383T1 CY1107383T1 CY20081100371T CY081100371T CY1107383T1 CY 1107383 T1 CY1107383 T1 CY 1107383T1 CY 20081100371 T CY20081100371 T CY 20081100371T CY 081100371 T CY081100371 T CY 081100371T CY 1107383 T1 CY1107383 T1 CY 1107383T1
- Authority
- CY
- Cyprus
- Prior art keywords
- physology
- suspensions
- solution
- enzymes
- compounds
- Prior art date
Links
- 239000000725 suspension Substances 0.000 title 1
- 102000015439 Phospholipases Human genes 0.000 abstract 1
- 108010064785 Phospholipases Proteins 0.000 abstract 1
- 108010058864 Phospholipases A2 Proteins 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 150000002475 indoles Chemical class 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- 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
- C07D403/02—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 two hetero rings
- C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33458801P | 2001-12-03 | 2001-12-03 | |
| US33460501P | 2001-12-03 | 2001-12-03 | |
| US33459101P | 2001-12-03 | 2001-12-03 | |
| US41966402P | 2002-10-18 | 2002-10-18 | |
| EP02786829A EP1451154B1 (en) | 2001-12-03 | 2002-12-02 | Inhibitors of cytosolic phospholipase a2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1107383T1 true CY1107383T1 (el) | 2012-12-19 |
Family
ID=27502498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY20081100371T CY1107383T1 (el) | 2001-12-03 | 2008-03-31 | Αναστολεις της φωσφολιπασης α2 του κυτοπλασμικου διαλυματος |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP1451154B1 (enExample) |
| JP (1) | JP4657605B2 (enExample) |
| KR (1) | KR100973665B1 (enExample) |
| CN (1) | CN100503566C (enExample) |
| AR (1) | AR037684A1 (enExample) |
| AT (1) | ATE384045T1 (enExample) |
| AU (1) | AU2002351182B2 (enExample) |
| BR (1) | BR0214672A (enExample) |
| CA (1) | CA2469138C (enExample) |
| CO (1) | CO5580763A2 (enExample) |
| CY (1) | CY1107383T1 (enExample) |
| DE (1) | DE60224707T2 (enExample) |
| DK (2) | DK1892239T3 (enExample) |
| EC (1) | ECSP045131A (enExample) |
| ES (2) | ES2401454T3 (enExample) |
| HU (1) | HUP0402577A3 (enExample) |
| IL (2) | IL162052A0 (enExample) |
| IN (1) | IN2005KO00312A (enExample) |
| NO (1) | NO327256B1 (enExample) |
| NZ (1) | NZ533269A (enExample) |
| PL (1) | PL370445A1 (enExample) |
| PT (1) | PT1451154E (enExample) |
| TW (1) | TWI334778B (enExample) |
| WO (1) | WO2003048122A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7713964B2 (en) | 2001-12-03 | 2010-05-11 | Wyeth Llc | Methods for treating asthmatic conditions |
| US7605156B2 (en) | 2001-12-03 | 2009-10-20 | Wyeth | Methods for the use of inhibitors of cytosolic phospholipase A2 |
| TW200510305A (en) * | 2003-07-25 | 2005-03-16 | Wyeth Corp | Process for the preparation of CPLA2 inhibitors |
| CN100548981C (zh) | 2003-11-17 | 2009-10-14 | 惠氏公司 | 制备n-取代的邻苯二甲酰亚胺的方法 |
| HN2004000536A (es) * | 2003-12-16 | 2009-02-18 | Wyeth Corp | Un procediemiento de sintesis para la alquilacion reductiva de la posicon c-3 de indoles |
| AR048239A1 (es) | 2004-02-25 | 2006-04-12 | Wyeth Corp | Procesos para la preparacion de haluros de aril- y heteroaril-alquilsulfonilo e intermediarios de sintesis de los mismos |
| US20050244367A1 (en) * | 2004-05-03 | 2005-11-03 | Ilypsa, Inc. | Phospholipase inhibitors localized in the gastrointestinal lumen |
| AR053410A1 (es) * | 2004-08-19 | 2007-05-09 | Wyeth Corp | Proceso para la sintesis de indoles n-alquilados c-2, c-3 sustituidos. compuestos intermediarios |
| ES2348920T3 (es) | 2005-04-13 | 2010-12-17 | Astion Development A/S | Agonistas de adrenoceptores beta-2 para el tratamiento de enfermedades del tejido conectivo de la piel. |
| TW200718687A (en) * | 2005-05-27 | 2007-05-16 | Wyeth Corp | Inhibitors of cytosolic phospholipase A2 |
| RU2466983C2 (ru) * | 2005-07-21 | 2012-11-20 | Вайет | Способ синтеза сульфонилгалогенидов и сульфонамидов из солей сульфоновых кислот |
| US7666898B2 (en) | 2005-11-03 | 2010-02-23 | Ilypsa, Inc. | Multivalent indole compounds and use thereof as phospholipase-A2 inhibitors |
| FR2899471A1 (fr) * | 2006-04-06 | 2007-10-12 | Pasteur Institut | Utilisation d'au moins un inhibiteur de la phospholipase a2 cytosolique comme medicament pour le traitement des maladies respiratoires |
| WO2007140317A2 (en) * | 2006-05-26 | 2007-12-06 | Wyeth | Use of inhibitors of cytosolic ph0sph0lipase a2 in the treatment of thrombosis |
| EP2077825A2 (en) * | 2006-10-31 | 2009-07-15 | Wyeth | Liquid formulations of phospholipase enzyme inhibitors |
| RU2009116423A (ru) * | 2006-10-31 | 2010-12-10 | Вайет (Us) | Композиции ингибиторов фермента фосфолипазы |
| JP5164972B2 (ja) * | 2007-03-29 | 2013-03-21 | 第一三共株式会社 | ｃＰＬＡ２阻害活性を有するインドール誘導体およびその用途並びに製造方法 |
| JP5198560B2 (ja) | 2008-04-28 | 2013-05-15 | 旭化成ファーマ株式会社 | フェニルプロピオン酸誘導体及びその用途 |
| WO2011047156A1 (en) * | 2009-10-15 | 2011-04-21 | Hercules Technology Management Co V, Inc. | Sepiapterin reductase inhibitors for the treatment of pain |
| WO2012031763A1 (en) | 2010-09-08 | 2012-03-15 | Twincore Zentrum Fuer Experimentelle Und Klinische Infektionsforschung Gmbh | Use of inhibitors of phospholipase a2 for the treatment or prevention of flavivirus infection |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2079374C (en) * | 1991-09-30 | 2003-08-05 | Merck Frosst Canada Incorporated | (bicyclic-azaarylmethoxy)indoles as inhibitors of leukotriene biosynthesis |
| US5994398A (en) * | 1996-12-11 | 1999-11-30 | Elan Pharmaceuticals, Inc. | Arylsulfonamides as phospholipase A2 inhibitors |
| EA003876B1 (ru) * | 1998-02-25 | 2003-10-30 | Дженетикс Инститьют, Ллс | Ингибиторы фосфолипазных ферментов |
| EE200000486A (et) * | 1998-02-25 | 2002-02-15 | Genetics Institute, Inc. | Fosfolipaasensüümide inhibiitorid, neid sisaldav farmatseutiline kompositsioon ning meetod põletikulise reaktsiooni raviks imetajal |
-
2002
- 2002-12-02 JP JP2003549314A patent/JP4657605B2/ja not_active Expired - Lifetime
- 2002-12-02 ES ES07023208T patent/ES2401454T3/es not_active Expired - Lifetime
- 2002-12-02 DE DE60224707T patent/DE60224707T2/de not_active Expired - Lifetime
- 2002-12-02 WO PCT/US2002/038311 patent/WO2003048122A2/en not_active Ceased
- 2002-12-02 TW TW091134928A patent/TWI334778B/zh not_active IP Right Cessation
- 2002-12-02 HU HU0402577A patent/HUP0402577A3/hu unknown
- 2002-12-02 DK DK07023208.7T patent/DK1892239T3/da active
- 2002-12-02 AU AU2002351182A patent/AU2002351182B2/en not_active Expired
- 2002-12-02 PL PL02370445A patent/PL370445A1/xx not_active Application Discontinuation
- 2002-12-02 AT AT02786829T patent/ATE384045T1/de active
- 2002-12-02 NZ NZ533269A patent/NZ533269A/xx not_active IP Right Cessation
- 2002-12-02 CN CNB028276116A patent/CN100503566C/zh not_active Expired - Lifetime
- 2002-12-02 PT PT02786829T patent/PT1451154E/pt unknown
- 2002-12-02 DK DK02786829T patent/DK1451154T3/da active
- 2002-12-02 IL IL16205202A patent/IL162052A0/xx unknown
- 2002-12-02 EP EP02786829A patent/EP1451154B1/en not_active Expired - Lifetime
- 2002-12-02 BR BR0214672-0A patent/BR0214672A/pt not_active Application Discontinuation
- 2002-12-02 CA CA2469138A patent/CA2469138C/en not_active Expired - Lifetime
- 2002-12-02 AR ARP020104643A patent/AR037684A1/es unknown
- 2002-12-02 ES ES02786829T patent/ES2300490T3/es not_active Expired - Lifetime
- 2002-12-02 KR KR1020047008482A patent/KR100973665B1/ko not_active Expired - Lifetime
-
2004
- 2004-05-19 IL IL162052A patent/IL162052A/en active IP Right Grant
- 2004-05-31 CO CO04050432A patent/CO5580763A2/es not_active Application Discontinuation
- 2004-06-03 EC EC2004005131A patent/ECSP045131A/es unknown
- 2004-06-25 NO NO20042679A patent/NO327256B1/no not_active IP Right Cessation
-
2005
- 2005-04-12 IN IN312KO2005 patent/IN2005KO00312A/en unknown
-
2008
- 2008-03-31 CY CY20081100371T patent/CY1107383T1/el unknown
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