HRP20090266T1 - Malonamide derivatives blocking the activity of gamma-secretase - Google Patents
Malonamide derivatives blocking the activity of gamma-secretaseInfo
- Publication number
- HRP20090266T1 HRP20090266T1 HR20090266T HRP20090266T HRP20090266T1 HR P20090266 T1 HRP20090266 T1 HR P20090266T1 HR 20090266 T HR20090266 T HR 20090266T HR P20090266 T HRP20090266 T HR P20090266T HR P20090266 T1 HRP20090266 T1 HR P20090266T1
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- halogen
- cycloalkyl
- hydrogen
- phenyl
- Prior art date
Links
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title 1
- 230000000903 blocking effect Effects 0.000 title 1
- 230000000694 effects Effects 0.000 title 1
- WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical class NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 title 1
- 229910052736 halogen Inorganic materials 0.000 abstract 8
- 150000002367 halogens Chemical group 0.000 abstract 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract 7
- 239000001257 hydrogen Substances 0.000 abstract 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 abstract 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 6
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- -1 C1-7-alkoxy Chemical class 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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
-
- 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
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/558—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/14—[b,f]-condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (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)
- Hydrogenated Pyridines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03019683 | 2003-09-09 | ||
PCT/EP2004/009700 WO2005023772A1 (en) | 2003-09-09 | 2004-08-31 | Malonamide derivatives blocking the activity of gama-secretase |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20090266T1 true HRP20090266T1 (en) | 2009-06-30 |
Family
ID=34224068
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20090266T HRP20090266T1 (en) | 2003-09-09 | 2009-05-12 | Malonamide derivatives blocking the activity of gamma-secretase |
Country Status (35)
Country | Link |
---|---|
US (1) | US7160875B2 (xx) |
EP (1) | EP1711470B1 (xx) |
JP (2) | JP4571639B2 (xx) |
KR (3) | KR100834177B1 (xx) |
CN (1) | CN100593539C (xx) |
AR (1) | AR045609A1 (xx) |
AT (1) | ATE428698T1 (xx) |
AU (1) | AU2004270361B2 (xx) |
BR (1) | BRPI0413533A (xx) |
CA (1) | CA2537440C (xx) |
CO (1) | CO5660268A2 (xx) |
CR (1) | CR8264A (xx) |
CY (1) | CY1109225T1 (xx) |
DE (1) | DE602004020680D1 (xx) |
DK (1) | DK1711470T3 (xx) |
EA (1) | EA009940B1 (xx) |
EC (1) | ECSP066414A (xx) |
ES (1) | ES2322652T3 (xx) |
HK (1) | HK1099014A1 (xx) |
HR (1) | HRP20090266T1 (xx) |
IL (1) | IL173905A (xx) |
MA (1) | MA28034A1 (xx) |
MX (1) | MXPA06002562A (xx) |
MY (1) | MY141308A (xx) |
NO (1) | NO20061047L (xx) |
NZ (1) | NZ545538A (xx) |
PL (1) | PL1711470T3 (xx) |
PT (1) | PT1711470E (xx) |
RS (1) | RS20060146A (xx) |
SI (1) | SI1711470T1 (xx) |
TN (1) | TNSN06077A1 (xx) |
TW (1) | TW200519092A (xx) |
UA (1) | UA83501C2 (xx) |
WO (1) | WO2005023772A1 (xx) |
ZA (1) | ZA200601989B (xx) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2514267C (en) * | 2003-02-04 | 2011-05-17 | F. Hoffmann-La Roche Ag | Malonamide derivatives as gamma-secretase inhibitors |
SI1711470T1 (sl) * | 2003-09-09 | 2009-08-31 | Hoffmann La Roche | Derivati malonamida, ki blokirajo aktivnost gama-sekretaze |
CN1894217B (zh) * | 2003-10-06 | 2011-09-21 | 弗·哈夫曼-拉罗切有限公司 | 用作γ-分泌酶抑制剂的取代的二苯并氮杂*和苯并二氮杂* |
US7211573B2 (en) | 2004-12-08 | 2007-05-01 | Hoffmann-La Roche Inc. | Malonamide derivatives |
RU2440342C2 (ru) * | 2006-03-27 | 2012-01-20 | Ф.Хоффманн-Ля Рош Аг | МАЛОНАМИДНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ γ-СЕКРЕТАЗЫ |
BRPI0717587A2 (pt) * | 2006-09-20 | 2013-10-29 | Hoffmann La Roche | Derivados de 4-oxo-2,3,4,5-tetra-hidro-benzo[b][1,4]diazepina |
MX2009007864A (es) * | 2007-02-02 | 2009-07-31 | Hoffmann La Roche | Derivados de 6-oxo-6,7-dihidro-5h-dibenzo[b,d]azepin-7-ilo. |
JP5148636B2 (ja) * | 2007-03-15 | 2013-02-20 | エフ.ホフマン−ラ ロシュ アーゲー | オレキシンアンタゴニストとしてのマロンアミド |
US7579464B2 (en) | 2007-05-25 | 2009-08-25 | Hoffmann-La Roche Inc. | Process for preparation of enantiomerically pure compounds |
MA33076B1 (fr) * | 2008-01-11 | 2012-03-01 | Hoffmann La Roche | Utilisation d'un inhibiteur de la gamma-secretase pour le traitement du cancer |
US8741889B2 (en) | 2008-01-11 | 2014-06-03 | Hoffmann-La Roche Inc | Method of treating non-small cell lung cancer and colon cancer with gamma-secretase inhibitor |
US8309299B2 (en) | 2010-05-19 | 2012-11-13 | Hoffmann-La Roche Inc. | Combination therapy and method for assessing resistance to treatment |
WO2012040444A2 (en) * | 2010-09-24 | 2012-03-29 | Bristol-Myers Squibb Company | Treatment of patients with incipient alzheimer's disease |
WO2012050370A2 (ko) * | 2010-10-15 | 2012-04-19 | 성균관대학교산학협력단 | 감마-세크레타제 저해제를 유효성분으로 함유하는 류마티스성 관절염의 예방 또는 치료용 조성물 |
KR101330184B1 (ko) | 2010-10-15 | 2013-11-15 | 성균관대학교산학협력단 | 감마-세크레타제 저해제를 유효성분으로 함유하는 류마티스성 관절염의 예방 또는 치료용 조성물 |
US20120114638A1 (en) | 2010-11-08 | 2012-05-10 | John Boylan | Combination therapy |
US20120184529A1 (en) | 2011-01-14 | 2012-07-19 | Demario Mark D | Combination therapy |
US20120225860A1 (en) | 2011-03-02 | 2012-09-06 | John Frederick Boylan | Method for administration of a gamma secretase inhibitor |
TWI530489B (zh) | 2011-03-22 | 2016-04-21 | 必治妥美雅史谷比公司 | 雙(氟烷基)-1,4-苯二氮呯酮化合物 |
AR087107A1 (es) | 2011-07-27 | 2014-02-12 | Lilly Co Eli | Compuesto inhibidor de la señalizacion de la trayectoria notch |
EP2897954B1 (en) | 2012-09-21 | 2016-10-26 | Bristol-Myers Squibb Company | Fluoroalkyl-1,4-benzodiazepinone compounds |
JP2015531792A (ja) | 2012-09-21 | 2015-11-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 1,4−ベンゾジアゼピノン化合物のプロドラッグ |
US9133126B2 (en) | 2012-09-21 | 2015-09-15 | Bristol-Myers Squibb Company | Fluoroalkyl dibenzoazepinone compounds |
US9187434B2 (en) | 2012-09-21 | 2015-11-17 | Bristol-Myers Squibb Company | Substituted 1,5-benzodiazepinones compounds |
JP2015533811A (ja) | 2012-09-21 | 2015-11-26 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | N−置換ビス(フルオロアルキル)1,4−ベンゾジアゼピノン化合物 |
CN105308030A (zh) | 2012-09-21 | 2016-02-03 | 百时美施贵宝公司 | 烷基、氟烷基-1,4-苯并二氮杂*酮化合物 |
WO2014047397A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Fluoroalkyl and fluorocycloalkyl 1,4-benzodiazepinone compounds as notch|inhibitors |
TWI614238B (zh) | 2012-09-21 | 2018-02-11 | 必治妥美雅史谷比公司 | 雙(氟烷基)-1,4-苯并二氮呯酮化合物及其前藥 |
WO2014047390A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Tricyclic heterocyclic compounds as notch inhibitors |
US9492469B2 (en) | 2013-04-04 | 2016-11-15 | Bristol-Myers Squibb Company | Combination therapy for the treatment of proliferative diseases |
EP2932966A1 (en) | 2014-04-16 | 2015-10-21 | Novartis AG | Gamma secretase inhibitors for treating respiratory diseases |
ES2751082T3 (es) * | 2015-10-30 | 2020-03-30 | Pipeline Therapeutics Inc | Compuestos de dibenzo azepina y su uso en el tratamiento de enfermedades y trastornos óticos |
RU2757276C2 (ru) * | 2016-12-16 | 2021-10-12 | Пайплайн Терапьютикс, Инк. | Способы лечения кохлеарной синаптопатии |
WO2018201056A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
US11161825B2 (en) * | 2017-08-15 | 2021-11-02 | Bayer Aktiengesellschaft | 4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-7-carboxamides |
PE20210320A1 (es) | 2018-06-01 | 2021-02-16 | Novartis Ag | Moleculas de union contra bcma y usos de las mismas |
WO2020261093A1 (en) | 2019-06-24 | 2020-12-30 | Novartis Ag | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
CN117881667A (zh) * | 2021-08-31 | 2024-04-12 | 巴斯夫欧洲公司 | 含有稠环系的除草剂丙二酰胺 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6632812B2 (en) * | 2000-04-11 | 2003-10-14 | Dupont Pharmaceuticals Company | Substituted lactams as inhibitors of Aβ protein production |
GB0012671D0 (en) * | 2000-05-24 | 2000-07-19 | Merck Sharp & Dohme | Therapeutic agents |
CA2514267C (en) * | 2003-02-04 | 2011-05-17 | F. Hoffmann-La Roche Ag | Malonamide derivatives as gamma-secretase inhibitors |
SI1711470T1 (sl) * | 2003-09-09 | 2009-08-31 | Hoffmann La Roche | Derivati malonamida, ki blokirajo aktivnost gama-sekretaze |
-
2004
- 2004-08-31 SI SI200431116T patent/SI1711470T1/sl unknown
- 2004-08-31 UA UAA200602854A patent/UA83501C2/uk unknown
- 2004-08-31 WO PCT/EP2004/009700 patent/WO2005023772A1/en active Application Filing
- 2004-08-31 AT AT04764665T patent/ATE428698T1/de active
- 2004-08-31 BR BRPI0413533-4A patent/BRPI0413533A/pt not_active Application Discontinuation
- 2004-08-31 KR KR1020067004763A patent/KR100834177B1/ko active IP Right Grant
- 2004-08-31 DE DE602004020680T patent/DE602004020680D1/de active Active
- 2004-08-31 KR KR1020077017457A patent/KR100838852B1/ko active IP Right Grant
- 2004-08-31 JP JP2006525701A patent/JP4571639B2/ja active Active
- 2004-08-31 CN CN200480032641A patent/CN100593539C/zh active Active
- 2004-08-31 ES ES04764665T patent/ES2322652T3/es active Active
- 2004-08-31 PT PT04764665T patent/PT1711470E/pt unknown
- 2004-08-31 KR KR1020077017458A patent/KR20070087233A/ko not_active Application Discontinuation
- 2004-08-31 PL PL04764665T patent/PL1711470T3/pl unknown
- 2004-08-31 EA EA200600503A patent/EA009940B1/ru not_active IP Right Cessation
- 2004-08-31 CA CA2537440A patent/CA2537440C/en not_active Expired - Fee Related
- 2004-08-31 MX MXPA06002562A patent/MXPA06002562A/es active IP Right Grant
- 2004-08-31 RS YUP-2006/0146A patent/RS20060146A/sr unknown
- 2004-08-31 NZ NZ545538A patent/NZ545538A/en not_active IP Right Cessation
- 2004-08-31 DK DK04764665T patent/DK1711470T3/da active
- 2004-08-31 AU AU2004270361A patent/AU2004270361B2/en not_active Ceased
- 2004-08-31 EP EP04764665A patent/EP1711470B1/en active Active
- 2004-09-02 US US10/933,177 patent/US7160875B2/en active Active
- 2004-09-06 MY MYPI20043603A patent/MY141308A/en unknown
- 2004-09-06 TW TW093126876A patent/TW200519092A/zh unknown
- 2004-09-08 AR ARP040103214A patent/AR045609A1/es not_active Application Discontinuation
-
2006
- 2006-02-23 CO CO06018272A patent/CO5660268A2/es not_active Application Discontinuation
- 2006-02-23 IL IL173905A patent/IL173905A/en active IP Right Grant
- 2006-03-01 CR CR8264A patent/CR8264A/es not_active Application Discontinuation
- 2006-03-03 NO NO20061047A patent/NO20061047L/no not_active Application Discontinuation
- 2006-03-07 TN TNP2006000077A patent/TNSN06077A1/fr unknown
- 2006-03-07 EC EC2006006414A patent/ECSP066414A/es unknown
- 2006-03-08 ZA ZA200601989A patent/ZA200601989B/en unknown
- 2006-03-10 MA MA28867A patent/MA28034A1/fr unknown
-
2007
- 2007-05-21 HK HK07105326.7A patent/HK1099014A1/xx not_active IP Right Cessation
-
2009
- 2009-05-12 HR HR20090266T patent/HRP20090266T1/xx unknown
- 2009-07-10 CY CY20091100729T patent/CY1109225T1/el unknown
-
2010
- 2010-06-18 JP JP2010138970A patent/JP2010229153A/ja active Pending
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