DK0749424T3 - Naphthalenderivater som prostaglandin-I2-agonister - Google Patents
Naphthalenderivater som prostaglandin-I2-agonisterInfo
- Publication number
- DK0749424T3 DK0749424T3 DK95910763T DK95910763T DK0749424T3 DK 0749424 T3 DK0749424 T3 DK 0749424T3 DK 95910763 T DK95910763 T DK 95910763T DK 95910763 T DK95910763 T DK 95910763T DK 0749424 T3 DK0749424 T3 DK 0749424T3
- Authority
- DK
- Denmark
- Prior art keywords
- prostaglandin
- agonists
- hydroxy
- naphthalene derivatives
- hydrogen
- Prior art date
Links
- 239000000556 agonist Substances 0.000 title 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 title 1
- 229960001123 epoprostenol Drugs 0.000 title 1
- 150000002790 naphthalenes Chemical class 0.000 title 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 4
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 239000001257 hydrogen Substances 0.000 abstract 3
- 125000002947 alkylene group Chemical group 0.000 abstract 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 2
- 150000002431 hydrogen Chemical group 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229910052736 halogen Chemical group 0.000 abstract 1
- 150000002367 halogens Chemical group 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Epoxy Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9404734A GB9404734D0 (en) | 1994-03-10 | 1994-03-10 | Heterocyclic compounds |
| GB9407036A GB9407036D0 (en) | 1994-04-08 | 1994-04-08 | Naphthalene derivatives |
| PCT/JP1995/000373 WO1995024393A1 (en) | 1994-03-10 | 1995-03-08 | Naphthalene derivatives as prostaglandin i2 agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK0749424T3 true DK0749424T3 (da) | 2001-11-26 |
Family
ID=26304472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK95910763T DK0749424T3 (da) | 1994-03-10 | 1995-03-08 | Naphthalenderivater som prostaglandin-I2-agonister |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US5763489A (enExample) |
| EP (1) | EP0749424B1 (enExample) |
| JP (1) | JP3245864B2 (enExample) |
| KR (1) | KR100383305B1 (enExample) |
| CN (1) | CN1057522C (enExample) |
| AT (1) | ATE205479T1 (enExample) |
| AU (1) | AU688871B2 (enExample) |
| CA (1) | CA2185104A1 (enExample) |
| DE (1) | DE69522676T2 (enExample) |
| DK (1) | DK0749424T3 (enExample) |
| ES (1) | ES2160156T3 (enExample) |
| GR (1) | GR3037080T3 (enExample) |
| HU (1) | HU224822B1 (enExample) |
| PT (1) | PT749424E (enExample) |
| RU (1) | RU2155188C2 (enExample) |
| TW (1) | TW282456B (enExample) |
| WO (1) | WO1995024393A1 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2179399A1 (en) * | 1993-12-20 | 1995-06-29 | Kiyoshi Taniguchi | 4,5-diaryloxazole derivatives |
| TW401408B (en) | 1995-07-21 | 2000-08-11 | Fujisawa Pharmaceutical Co | Heterocyclic compounds having prostaglandin I2 agonism |
| DE19537548A1 (de) * | 1995-10-09 | 1997-04-10 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
| DE19604191A1 (de) * | 1996-02-06 | 1997-08-07 | Hoechst Schering Agrevo Gmbh | 2,4-Diamino-1,3,5-triazine, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| AUPO713297A0 (en) * | 1997-06-02 | 1997-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Oxazole compound |
| GB9720270D0 (en) | 1997-09-25 | 1997-11-26 | Pharmagene Lab Limited | Medicaments for the treatment of migraine |
| AUPP003297A0 (en) | 1997-10-27 | 1997-11-20 | Fujisawa Pharmaceutical Co., Ltd. | 4,5-diaryloxazole compounds |
| AUPP029197A0 (en) * | 1997-11-10 | 1997-12-04 | Fujisawa Pharmaceutical Co., Ltd. | Benzocycloheptene derivatives |
| AUPP109097A0 (en) | 1997-12-22 | 1998-01-22 | Fujisawa Pharmaceutical Co., Ltd. | Napthalene derivatives |
| US6335459B1 (en) | 1998-12-23 | 2002-01-01 | Syntex (U.S.A.) Llc | Aryl carboxylic acid and aryl tetrazole derivatives as IP receptor modulators |
| CN1370079A (zh) * | 1999-06-21 | 2002-09-18 | 藤泽药品工业株式会社 | 皮肤溃疡治疗剂 |
| US20040127529A1 (en) * | 1999-06-21 | 2004-07-01 | Fujisawa Pharmaceutical Co., Ltd. | Remedies for skin ulcer |
| WO2002042243A1 (fr) * | 2000-11-21 | 2002-05-30 | Fujisawa Pharmaceutical Co., Ltd | Processus de preparation de derives de tetrahydronaphtalene |
| JPWO2002085412A1 (ja) * | 2001-04-18 | 2004-08-05 | 藤沢薬品工業株式会社 | 組織線維化抑制剤 |
| US20060217421A1 (en) | 2003-05-09 | 2006-09-28 | Hajimu Kurumatani | Fortifier |
| TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | 1,4-二取代之3-氰基-吡啶酮衍生物及其作為mGluR2-受體之正向異位性調節劑之用途 |
| PL2094662T3 (pl) | 2006-12-14 | 2012-09-28 | Astellas Pharma Inc | Związki oparte na policyklicznych kwasach użyteczne jako antagoniści rCRTH2 oraz jako środki przeciwalergiczne |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| EP2203439B1 (en) | 2007-09-14 | 2011-01-26 | Ortho-McNeil-Janssen Pharmaceuticals, Inc. | 1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h, 1'h-ý1, 4'¨bipyridinyl-2'-ones |
| EP2280696B9 (en) | 2008-03-18 | 2015-12-09 | Arena Pharmaceuticals, Inc. | Modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto |
| MX2011002042A (es) | 2008-09-02 | 2011-06-20 | Ortho Mcneil Janssen Pharm | Derivados de 3-azabiciclo[3.1.o]hexilo como moduladores de los receptores del glutamato metabotropico. |
| WO2010060589A1 (en) | 2008-11-28 | 2010-06-03 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
| EP2430022B1 (en) | 2009-05-12 | 2013-11-20 | Janssen Pharmaceuticals, Inc. | 1,2,4-Triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
| JP5707390B2 (ja) | 2009-05-12 | 2015-04-30 | ジャンセン ファーマシューティカルズ, インコーポレイテッド | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| WO2012062750A1 (en) | 2010-11-08 | 2012-05-18 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| CA2814998C (en) | 2010-11-08 | 2019-10-29 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| ME03518B (me) | 2014-01-21 | 2020-04-20 | Janssen Pharmaceutica Nv | Kombinacije koje obuhvataju pozitivne alosterične modulatore ili ortosterične agoniste metabotropnog glutamatergičnog receptora podtipa 2 i njihova primjena |
| AU2015208233B2 (en) | 2014-01-21 | 2019-08-29 | Janssen Pharmaceutica Nv | Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use |
| CN110582271B (zh) | 2017-03-01 | 2022-06-14 | 阿瑞那制药公司 | 包含pgi2受体激动剂的组合物及其制备方法 |
| AU2023222747A1 (en) | 2022-02-15 | 2024-08-22 | United Therapeutics Corporation | Crystalline prostacyclin (ip) receptor agonist and uses thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1366514A1 (ru) * | 1986-01-28 | 1988-01-15 | Днепропетровский химико-технологический институт им.Ф.Э.Дзержинского | Способ получени производных N-арил-5-ариламидо-4,6-диметилпиридона-2 |
| DE3837809A1 (de) * | 1988-11-08 | 1990-05-10 | Merck Patent Gmbh | Tetralinderivate |
| US5344836A (en) * | 1991-11-11 | 1994-09-06 | Ono Pharmaceutical Co., Ltd. | Fused benzeneoxyacetic acid derivatives |
-
1995
- 1995-03-08 JP JP52335695A patent/JP3245864B2/ja not_active Expired - Fee Related
- 1995-03-08 CA CA002185104A patent/CA2185104A1/en not_active Abandoned
- 1995-03-08 US US08/702,546 patent/US5763489A/en not_active Expired - Fee Related
- 1995-03-08 PT PT95910763T patent/PT749424E/pt unknown
- 1995-03-08 RU RU96120174/04A patent/RU2155188C2/ru not_active IP Right Cessation
- 1995-03-08 ES ES95910763T patent/ES2160156T3/es not_active Expired - Lifetime
- 1995-03-08 HU HU9602466A patent/HU224822B1/hu not_active IP Right Cessation
- 1995-03-08 DK DK95910763T patent/DK0749424T3/da active
- 1995-03-08 AT AT95910763T patent/ATE205479T1/de not_active IP Right Cessation
- 1995-03-08 TW TW084102192A patent/TW282456B/zh active
- 1995-03-08 CN CN95192846A patent/CN1057522C/zh not_active Expired - Fee Related
- 1995-03-08 DE DE69522676T patent/DE69522676T2/de not_active Expired - Fee Related
- 1995-03-08 WO PCT/JP1995/000373 patent/WO1995024393A1/en not_active Ceased
- 1995-03-08 KR KR1019960704963A patent/KR100383305B1/ko not_active Expired - Fee Related
- 1995-03-08 AU AU18618/95A patent/AU688871B2/en not_active Ceased
- 1995-03-08 EP EP95910763A patent/EP0749424B1/en not_active Expired - Lifetime
-
1998
- 1998-02-23 US US09/028,861 patent/US5863918A/en not_active Expired - Fee Related
-
2001
- 2001-10-31 GR GR20010401952T patent/GR3037080T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR970701698A (ko) | 1997-04-12 |
| US5763489A (en) | 1998-06-09 |
| DE69522676D1 (de) | 2001-10-18 |
| JP3245864B2 (ja) | 2002-01-15 |
| AU688871B2 (en) | 1998-03-19 |
| RU2155188C2 (ru) | 2000-08-27 |
| HU9602466D0 (en) | 1996-11-28 |
| PT749424E (pt) | 2002-03-28 |
| HUT75226A (en) | 1997-04-28 |
| CN1057522C (zh) | 2000-10-18 |
| ATE205479T1 (de) | 2001-09-15 |
| DE69522676T2 (de) | 2002-04-18 |
| EP0749424B1 (en) | 2001-09-12 |
| WO1995024393A1 (en) | 1995-09-14 |
| ES2160156T3 (es) | 2001-11-01 |
| EP0749424A1 (en) | 1996-12-27 |
| JPH09509958A (ja) | 1997-10-07 |
| KR100383305B1 (ko) | 2003-11-01 |
| HU224822B1 (en) | 2006-02-28 |
| AU1861895A (en) | 1995-09-25 |
| TW282456B (enExample) | 1996-08-01 |
| HK1013289A1 (en) | 1999-08-20 |
| CN1147250A (zh) | 1997-04-09 |
| CA2185104A1 (en) | 1995-09-14 |
| US5863918A (en) | 1999-01-26 |
| GR3037080T3 (en) | 2002-01-31 |
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