EP1196194A2 - COMBINAISON D'INHIBITEURS DE MTP (PROTEINE DE TRANSFERT MICROSOMALE) ET INHIBITEURS DE HMG-CoA-REDUCTASE ET LEUR UTILISATION DANS DES MEDICAMENTS - Google Patents
COMBINAISON D'INHIBITEURS DE MTP (PROTEINE DE TRANSFERT MICROSOMALE) ET INHIBITEURS DE HMG-CoA-REDUCTASE ET LEUR UTILISATION DANS DES MEDICAMENTSInfo
- Publication number
- EP1196194A2 EP1196194A2 EP00942056A EP00942056A EP1196194A2 EP 1196194 A2 EP1196194 A2 EP 1196194A2 EP 00942056 A EP00942056 A EP 00942056A EP 00942056 A EP00942056 A EP 00942056A EP 1196194 A2 EP1196194 A2 EP 1196194A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- carbon atoms
- chain
- straight
- branched alkyl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 27
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title claims abstract description 25
- 239000003112 inhibitor Substances 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title claims description 15
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 203
- 125000000217 alkyl group Chemical group 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 82
- 229910052736 halogen Inorganic materials 0.000 claims description 60
- 150000002367 halogens Chemical class 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000003545 alkoxy group Chemical group 0.000 claims description 52
- -1 carboxy, hydroxy Chemical group 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
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- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 5
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- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 4
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 4
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- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 claims description 3
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- 125000003435 aroyl group Chemical group 0.000 claims description 2
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- KIMRCJZMVARVSU-UHFFFAOYSA-N 2-cyclopentyl-2-[4-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n-(2-hydroxy-1-phenylethyl)acetamide Chemical compound C12=NC(C)=CC(C)=C2C2=CC=CC=C2N1CC(C=C1)=CC=C1C(C(=O)NC(CO)C=1C=CC=CC=1)C1CCCC1 KIMRCJZMVARVSU-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- T represents a nitrogen atom or the -CH group
- T, V, X and Y are the same or different and represent an oxygen or sulfur atom
- A, D, E, G, L and M are the same or different and represent hydrogen, halogen, trifluoromethyl, carboxy, hydroxy, straight-chain or branched alkoxy or alkoxycarbonyl each having up to 6 carbon atoms or straight-chain or branched alkyl having up to 6 carbon atoms which in turn can be substituted by hydroxyl or by straight-chain or branched alkoxy having up to 4 carbon atoms
- Rl and R 2 are the same or different and represent hydrogen, cycloalkyl having 3 to 8 carbon atoms or straight-chain or branched alkyl having up to 10 carbon atoms, which is optionally substituted by cycloalkyl having 3 to 6 carbon atoms, or represent phenyl, which is optionally substituted by Halogen or trifluoromethyl is substituted, or
- physiologically acceptable salts of the MTP inhibitors listed above is also claimed.
- physiologically acceptable salts of the compounds according to the invention are e.g.
- Statins are usually used as lactones (see, for example, lovastatin), esters or as carboxylic acids or as salts of the carboxylic acid (see, for example, cerivastatin sodium).
- the statins can be used in all suitable forms, ie in the form of the respective salts, hydrates, alcoholates, esters, lactones and tautomers.
- atorvastatin and in particular cerivastatin and their respective salts, hydrates, alcoholates, esters, lactones and tautomers are very particularly preferred.
- Lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid or mixed salts thereof can also be salts with customary bases, such as, for example, alkali metal salts (for example sodium or potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts derived from ammonia or organic amines such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, Procaine, dibenzylamine, N-methylmo ⁇ holin, dihydro-abietylamine, 1-ephenamine or methyl-piperidine and mixed salts thereof.
- customary bases such as, for example, alkali metal salts (for example sodium or potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts derived from ammonia or organic amines such as, for example, diethylamine, triethylamine, e
- MTP inhibitors are the compounds listed in the table below.
- the combinations according to the invention are well tolerated and are effective even in low doses, a wide variety of formulation variants can be implemented.
- the two individual components A and B do not necessarily have to be taken at the same time; staggered intake may be beneficial to achieve optimal effects.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L'invention concerne l'utilisation d'une combinaison d'au moins un inhibiteur de MTP (constituant A) sélectionné et d'un inhibiteur de HMG-CoA-réductase (constituant B) pour lutter contre des maladies cardio-vasculaires. L'invention concerne également des médicaments contenant ladite combinaison et leur préparation.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19929065A DE19929065A1 (de) | 1999-06-25 | 1999-06-25 | Kombination von MTP-Inhibitoren und HMG-CoA-Reduktase-Inhibitoren und ihre Verwendung in Arzneimitteln |
| DE19929065 | 1999-06-25 | ||
| PCT/EP2000/005410 WO2001000183A2 (fr) | 1999-06-25 | 2000-06-13 | COMBINAISON D'INHIBITEURS DE MTP (PROTEINE DE TRANSFERT MICROSOMALE) ET INHIBITEURS DE HMG-CoA-REDUCTASE ET LEUR UTILISATION DANS DES MEDICAMENTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1196194A2 true EP1196194A2 (fr) | 2002-04-17 |
Family
ID=7912459
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00942056A Withdrawn EP1196194A2 (fr) | 1999-06-25 | 2000-06-13 | COMBINAISON D'INHIBITEURS DE MTP (PROTEINE DE TRANSFERT MICROSOMALE) ET INHIBITEURS DE HMG-CoA-REDUCTASE ET LEUR UTILISATION DANS DES MEDICAMENTS |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1196194A2 (fr) |
| JP (1) | JP2003503342A (fr) |
| AR (1) | AR028996A1 (fr) |
| AU (1) | AU5680900A (fr) |
| CA (1) | CA2376881A1 (fr) |
| DE (1) | DE19929065A1 (fr) |
| DO (1) | DOP2000000022A (fr) |
| GT (1) | GT200000099A (fr) |
| PE (1) | PE20010302A1 (fr) |
| SV (1) | SV2004000109A (fr) |
| UY (1) | UY26218A1 (fr) |
| WO (1) | WO2001000183A2 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053927A (zh) * | 2018-08-08 | 2018-12-21 | 中山大学 | 一种含维生素b12基团的两亲性海藻酸钠衍生物及其制备方法和应用 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10030375A1 (de) * | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| CN101838218A (zh) * | 2002-02-28 | 2010-09-22 | 日本烟草产业株式会社 | 酯化合物及其医药用途 |
| WO2005021486A1 (fr) | 2003-08-29 | 2005-03-10 | Japan Tobacco Inc. | Derive d'ester et utilisation medicale de celui-ci |
| US8101774B2 (en) | 2004-10-18 | 2012-01-24 | Japan Tobacco Inc. | Ester derivatives and medicinal use thereof |
| FR2884831B1 (fr) * | 2005-04-22 | 2007-08-10 | Merck Sante Soc Par Actions Si | Methode de criblage de composes inhibiteurs de la mtp |
| DE102011007272A1 (de) | 2011-04-13 | 2012-10-18 | Bayer Pharma Aktiengesellschaft | Verzweigte 3-Phenylpropionsäure-Derivate und ihre Verwendung |
| US10905667B2 (en) | 2018-07-24 | 2021-02-02 | Bayer Pharma Aktiengesellschaft | Orally administrable modified-release pharmaceutical dosage form |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4435477A1 (de) * | 1994-10-04 | 1996-04-11 | Bayer Ag | Cycloalkano-indol- und -azaindol-derivate |
| DE19546919A1 (de) * | 1995-12-15 | 1997-06-19 | Bayer Ag | N-Heterocyclisch substituierte Phenylessigsäure-Derivate |
| DE19546918A1 (de) * | 1995-12-15 | 1997-06-19 | Bayer Ag | Bicyclische Heterocyclen |
| DE19615265A1 (de) * | 1996-04-18 | 1997-12-04 | Bayer Ag | Neue Pyridazino-, Pyrimido-, Pyrazino- und Triazino-indole |
| CA2272719C (fr) * | 1996-11-27 | 2002-10-01 | Pfizer Limited | Amides inhibant la secretion d'apo b et/ou la proteine mtp |
| EP1024804A4 (fr) * | 1997-05-01 | 2001-03-21 | Bristol Myers Squibb Co | Combinaisons therapeutiques d'inhibiteur de mtp et de vitamine liposoluble destinees a reduire les taux de lipides seriques |
-
1999
- 1999-06-25 DE DE19929065A patent/DE19929065A1/de not_active Withdrawn
-
2000
- 2000-06-13 WO PCT/EP2000/005410 patent/WO2001000183A2/fr not_active Ceased
- 2000-06-13 JP JP2001505893A patent/JP2003503342A/ja active Pending
- 2000-06-13 AU AU56809/00A patent/AU5680900A/en not_active Abandoned
- 2000-06-13 CA CA002376881A patent/CA2376881A1/fr not_active Abandoned
- 2000-06-13 EP EP00942056A patent/EP1196194A2/fr not_active Withdrawn
- 2000-06-21 GT GT200000099A patent/GT200000099A/es unknown
- 2000-06-22 AR ARP000103129A patent/AR028996A1/es unknown
- 2000-06-23 PE PE2000000625A patent/PE20010302A1/es not_active Application Discontinuation
- 2000-06-23 SV SV2000000109A patent/SV2004000109A/es unknown
- 2000-06-23 UY UY26218A patent/UY26218A1/es not_active Application Discontinuation
-
2008
- 2008-04-11 DO DO2000000022A patent/DOP2000000022A/es unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0100183A2 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053927A (zh) * | 2018-08-08 | 2018-12-21 | 中山大学 | 一种含维生素b12基团的两亲性海藻酸钠衍生物及其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| DOP2000000022A (es) | 2008-08-15 |
| DE19929065A1 (de) | 2000-12-28 |
| AR028996A1 (es) | 2003-06-04 |
| UY26218A1 (es) | 2001-01-31 |
| AU5680900A (en) | 2001-01-31 |
| WO2001000183A2 (fr) | 2001-01-04 |
| GT200000099A (es) | 2001-12-13 |
| SV2004000109A (es) | 2004-05-07 |
| PE20010302A1 (es) | 2001-04-12 |
| CA2376881A1 (fr) | 2001-01-04 |
| WO2001000183A3 (fr) | 2001-05-10 |
| JP2003503342A (ja) | 2003-01-28 |
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