EE05168B1 - N-guanidinoalklamiid, meetod selle valmistamiseks, seda sisaldav farmatseutiline preparaat ning raviotstarbeline kasutamine - Google Patents
N-guanidinoalklamiid, meetod selle valmistamiseks, seda sisaldav farmatseutiline preparaat ning raviotstarbeline kasutamineInfo
- Publication number
- EE05168B1 EE05168B1 EEP200200199A EEP200200199A EE05168B1 EE 05168 B1 EE05168 B1 EE 05168B1 EE P200200199 A EEP200200199 A EE P200200199A EE P200200199 A EEP200200199 A EE P200200199A EE 05168 B1 EE05168 B1 EE 05168B1
- Authority
- EE
- Estonia
- Prior art keywords
- preparation
- guanidinoalkamide
- therapeutic use
- pharmaceutical preparation
- preparation containing
- Prior art date
Links
- 238000000034 method Methods 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- 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
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99121623A EP1095933A1 (en) | 1999-10-30 | 1999-10-30 | Novel N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them |
| PCT/EP2000/010395 WO2001032611A1 (en) | 1999-10-30 | 2000-10-21 | N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EE200200199A EE200200199A (et) | 2003-06-16 |
| EE05168B1 true EE05168B1 (et) | 2009-06-15 |
Family
ID=8239305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EEP200200199A EE05168B1 (et) | 1999-10-30 | 2000-10-21 | N-guanidinoalklamiid, meetod selle valmistamiseks, seda sisaldav farmatseutiline preparaat ning raviotstarbeline kasutamine |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US6472562B1 (https=) |
| EP (2) | EP1095933A1 (https=) |
| JP (1) | JP4658430B2 (https=) |
| KR (1) | KR100981593B1 (https=) |
| CN (1) | CN1249026C (https=) |
| AR (1) | AR026257A1 (https=) |
| AT (1) | ATE264837T1 (https=) |
| AU (1) | AU776797B2 (https=) |
| BR (1) | BR0015186A (https=) |
| CA (1) | CA2389412C (https=) |
| CZ (1) | CZ301855B6 (https=) |
| DE (1) | DE60010113T2 (https=) |
| DK (1) | DK1228039T3 (https=) |
| EE (1) | EE05168B1 (https=) |
| ES (1) | ES2220553T3 (https=) |
| HR (1) | HRP20020372B1 (https=) |
| HU (1) | HUP0203627A3 (https=) |
| IL (2) | IL149209A0 (https=) |
| ME (1) | MEP54708A (https=) |
| MX (1) | MXPA02003805A (https=) |
| NO (1) | NO328016B1 (https=) |
| NZ (1) | NZ518607A (https=) |
| PL (1) | PL203859B1 (https=) |
| PT (1) | PT1228039E (https=) |
| RS (1) | RS50471B (https=) |
| RU (1) | RU2253651C2 (https=) |
| SI (1) | SI1228039T1 (https=) |
| SK (1) | SK286856B6 (https=) |
| TR (1) | TR200201181T2 (https=) |
| WO (1) | WO2001032611A1 (https=) |
| ZA (1) | ZA200203294B (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4579240B2 (ja) * | 2003-07-04 | 2010-11-10 | ロンザ アーゲー | 担持相合成法の改善 |
| KR102069498B1 (ko) | 2007-09-28 | 2020-01-23 | 포톨라 파마슈티컬스, 인코포레이티드 | 인자 Xa 저해제에 대한 안티도트 및 그것을 사용하는 방법 |
| EP3613743B1 (en) | 2008-01-04 | 2022-03-16 | Intellikine, LLC | Processes for the preparation of 1h-pyrazolo[3,4-d]pyrimidin-4-amine derivatives |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| RU2377990C1 (ru) * | 2008-07-23 | 2010-01-10 | Федеральное Государственное Образовательное Учреждение Высшего Профессионального Образования "Южный Федеральный Университет" | Антитромботическое средство, влияющее на регуляцию функциональной активности тромбоцитов |
| EP2364165B1 (en) | 2008-11-14 | 2018-01-03 | Portola Pharmaceuticals, Inc. | Antidotes for factor xa inhibitors and methods of using the same in combination with blood coagulating agents |
| PL3604510T3 (pl) | 2009-03-30 | 2025-07-28 | Alexion Pharmaceuticals, Inc. | Antidota na inhibitory czynnika xa i sposoby ich stosowania |
| PT2453910T (pt) | 2009-07-15 | 2016-12-07 | Portola Pharm Inc | Formulação de dose unitária de antídoto contra inibidores de fator xa para uso na prevenção de sangramento |
| TWI674262B (zh) | 2011-01-10 | 2019-10-11 | 美商英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| EP2914296B2 (en) | 2012-11-01 | 2021-09-29 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| RU2754507C2 (ru) | 2016-06-24 | 2021-09-02 | Инфинити Фармасьютикалз, Инк. | Комбинированная терапия |
| CN110357800B (zh) * | 2018-04-09 | 2022-07-26 | 青岛海生洋润生物科技有限公司 | 脯氨酸衍生物及其在制备治疗心脑血管疾病药物中的应用 |
| CN115317474A (zh) * | 2021-05-10 | 2022-11-11 | 中国海洋大学 | 一种苯酰胍衍生物在用于制备预防和治疗神经系统疾病或心血管系统疾病的药物中的应用 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU206372B (en) * | 1990-09-03 | 1992-10-28 | Richter Gedeon Vegyeszet | Process for producing new oligopeptides which selectively inhibit proliferation of haemopoietic cells and pharmaceutical compositions comprising same |
| US5506134A (en) | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| US5833982A (en) | 1991-02-28 | 1998-11-10 | Zymogenetics, Inc. | Modified factor VII |
| US5788965A (en) | 1991-02-28 | 1998-08-04 | Novo Nordisk A/S | Modified factor VII |
| US5371072A (en) * | 1992-10-16 | 1994-12-06 | Corvas International, Inc. | Asp-Pro-Arg α-keto-amide enzyme inhibitors |
| DE4326465A1 (de) | 1993-01-20 | 1995-02-09 | Thomae Gmbh Dr K | Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| JPH08506225A (ja) | 1993-01-20 | 1996-07-02 | ジョン アリグザンドロビクス,ピーター | ラインモニタシステム |
| US5525623A (en) * | 1993-03-12 | 1996-06-11 | Arris Pharmaceutical Corporation | Compositions and methods for the treatment of immunomediated inflammatory disorders |
| SI9520044B (sl) | 1994-04-26 | 2004-08-31 | Aventis Pharmaceuticals Inc. | Inhibitorji Xa faktorja |
| DE69529770T2 (de) * | 1994-12-02 | 2003-12-24 | Yamanouchi Pharmaceutical Co., Ltd. | Neues amidinonaphthylderivat oder dessen salz |
| US6342504B1 (en) * | 1994-12-13 | 2002-01-29 | Corvas International, Inc. | Aromatic heterocyclic derivatives as enzyme inhibitors |
| EP1020434A4 (en) * | 1997-08-27 | 2000-11-15 | Kissei Pharmaceutical | 3-AMIDINOANILINE DERIVATIVES, INHIBITORS OF THE ACTIVATED BLOOD COINTENANCE FACTOR X AND INTERMEDIATE PRODUCTS FOR PRODUCING BOTH |
| SE9703414D0 (sv) * | 1997-09-23 | 1997-09-23 | Astra Ab | New compounds |
| HU227568B1 (en) | 1997-12-24 | 2011-08-29 | Sanofi Aventis Deutschland | Indole derivatives, as inhibitors os factor xa |
| AU2074699A (en) * | 1998-01-26 | 1999-08-09 | Yamanouchi Pharmaceutical Co., Ltd. | Novel benzene-fused heterocyclic derivatives or salts thereof |
| EP0987274A1 (en) | 1998-09-15 | 2000-03-22 | Hoechst Marion Roussel Deutschland GmbH | Factor VIIa Inhibitors |
| ES2226839T3 (es) * | 1999-05-05 | 2005-04-01 | MERCK & CO., INC. | Nuevos catecoles como agentes antimicrobianos. |
-
1999
- 1999-10-30 EP EP99121623A patent/EP1095933A1/en not_active Withdrawn
-
2000
- 2000-10-21 IL IL14920900A patent/IL149209A0/xx active IP Right Grant
- 2000-10-21 RS YUP-297/02A patent/RS50471B/sr unknown
- 2000-10-21 CA CA002389412A patent/CA2389412C/en not_active Expired - Fee Related
- 2000-10-21 JP JP2001534764A patent/JP4658430B2/ja not_active Expired - Fee Related
- 2000-10-21 BR BR0015186-6A patent/BR0015186A/pt active Search and Examination
- 2000-10-21 DK DK00971396T patent/DK1228039T3/da active
- 2000-10-21 WO PCT/EP2000/010395 patent/WO2001032611A1/en not_active Ceased
- 2000-10-21 MX MXPA02003805A patent/MXPA02003805A/es active IP Right Grant
- 2000-10-21 NZ NZ518607A patent/NZ518607A/en not_active IP Right Cessation
- 2000-10-21 PL PL354808A patent/PL203859B1/pl not_active IP Right Cessation
- 2000-10-21 AT AT00971396T patent/ATE264837T1/de active
- 2000-10-21 ES ES00971396T patent/ES2220553T3/es not_active Expired - Lifetime
- 2000-10-21 DE DE60010113T patent/DE60010113T2/de not_active Expired - Lifetime
- 2000-10-21 ME MEP-547/08A patent/MEP54708A/xx unknown
- 2000-10-21 HR HR20020372A patent/HRP20020372B1/xx not_active IP Right Cessation
- 2000-10-21 RU RU2002114041/04A patent/RU2253651C2/ru not_active IP Right Cessation
- 2000-10-21 EP EP00971396A patent/EP1228039B1/en not_active Expired - Lifetime
- 2000-10-21 AU AU10265/01A patent/AU776797B2/en not_active Ceased
- 2000-10-21 CN CNB008151407A patent/CN1249026C/zh not_active Expired - Fee Related
- 2000-10-21 HU HU0203627A patent/HUP0203627A3/hu unknown
- 2000-10-21 PT PT00971396T patent/PT1228039E/pt unknown
- 2000-10-21 SI SI200030422T patent/SI1228039T1/xx unknown
- 2000-10-21 CZ CZ20021489A patent/CZ301855B6/cs not_active IP Right Cessation
- 2000-10-21 EE EEP200200199A patent/EE05168B1/xx not_active IP Right Cessation
- 2000-10-21 TR TR2002/01181T patent/TR200201181T2/xx unknown
- 2000-10-21 SK SK578-2002A patent/SK286856B6/sk not_active IP Right Cessation
- 2000-10-26 AR ARP000105647A patent/AR026257A1/es active IP Right Grant
- 2000-10-27 US US09/697,188 patent/US6472562B1/en not_active Expired - Lifetime
-
2002
- 2002-04-18 IL IL149209A patent/IL149209A/en not_active IP Right Cessation
- 2002-04-25 ZA ZA200203294A patent/ZA200203294B/xx unknown
- 2002-04-29 NO NO20022022A patent/NO328016B1/no not_active IP Right Cessation
- 2002-04-29 KR KR1020027005515A patent/KR100981593B1/ko not_active Expired - Fee Related
- 2002-08-26 US US10/227,222 patent/US6664393B2/en not_active Expired - Lifetime
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