SI3389727T1 - Radioaktivno označeni ligandi PET MGLUR2/3 - Google Patents
Radioaktivno označeni ligandi PET MGLUR2/3Info
- Publication number
- SI3389727T1 SI3389727T1 SI201630916T SI201630916T SI3389727T1 SI 3389727 T1 SI3389727 T1 SI 3389727T1 SI 201630916 T SI201630916 T SI 201630916T SI 201630916 T SI201630916 T SI 201630916T SI 3389727 T1 SI3389727 T1 SI 3389727T1
- Authority
- SI
- Slovenia
- Prior art keywords
- pet ligands
- mglur2
- radiolabelled
- radiolabelled mglur2
- ligands
- Prior art date
Links
- 239000003446 ligand Substances 0.000 title 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- 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
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15201240 | 2015-12-18 | ||
| PCT/EP2016/081542 WO2017103182A1 (en) | 2015-12-18 | 2016-12-16 | Radiolabelled mglur2/3 pet ligands |
| EP16812961.7A EP3389727B1 (en) | 2015-12-18 | 2016-12-16 | Radiolabelled mglur2/3 pet ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI3389727T1 true SI3389727T1 (sl) | 2020-10-30 |
Family
ID=55023944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201630916T SI3389727T1 (sl) | 2015-12-18 | 2016-12-16 | Radioaktivno označeni ligandi PET MGLUR2/3 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US11033641B2 (sl) |
| EP (1) | EP3389727B1 (sl) |
| JP (1) | JP6927974B2 (sl) |
| AU (1) | AU2016374571B2 (sl) |
| CA (1) | CA3003998A1 (sl) |
| CY (1) | CY1124935T1 (sl) |
| DK (1) | DK3389727T3 (sl) |
| ES (1) | ES2828976T3 (sl) |
| HR (1) | HRP20201372T1 (sl) |
| HU (1) | HUE050665T2 (sl) |
| LT (1) | LT3389727T (sl) |
| PL (1) | PL3389727T3 (sl) |
| PT (1) | PT3389727T (sl) |
| RS (1) | RS60981B1 (sl) |
| SI (1) | SI3389727T1 (sl) |
| SM (1) | SMT202000591T1 (sl) |
| WO (1) | WO2017103182A1 (sl) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JOP20150177B1 (ar) | 2014-08-01 | 2021-08-17 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| JOP20150179B1 (ar) | 2014-08-01 | 2021-08-17 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| ES2727379T3 (es) | 2014-12-03 | 2019-10-15 | Janssen Pharmaceutica Nv | Compuestos de 6,7-dihidropirazolo[1,5-a]pirazin-4(5H)-ona y su uso como moduladores alostéricos negativos de receptores de mGlu2 |
| US10967078B2 (en) | 2014-12-03 | 2021-04-06 | Janssen Pharmaceutica Nv | Radiolabelled mGluR2 PET ligands |
| SI3389727T1 (sl) | 2015-12-18 | 2020-10-30 | Janssen Pharmaceutica Nv | Radioaktivno označeni ligandi PET MGLUR2/3 |
| EP3389728B1 (en) | 2015-12-18 | 2020-08-05 | Janssen Pharmaceutica NV | Radiolabelled mglur2/3 pet ligands |
| EP3719023B1 (en) | 2017-11-24 | 2024-10-16 | Sumitomo Pharma Co., Ltd. | 6,7-DIHYDROPYRAZOLO[1,5-a]PYRAZINONE DERIVATIVE AND MEDICAL USE THEREOF |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0756200B1 (en) | 1995-07-26 | 1999-11-10 | Konica Corporation | Silver halide color photographic light-sensitive material |
| US6482821B2 (en) | 1996-12-20 | 2002-11-19 | Hoechst Aktiengellschaft | Vitronectin receptor antagonists, their preparation and their use |
| DE19653647A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
| US6831074B2 (en) | 2001-03-16 | 2004-12-14 | Pfizer Inc | Pharmaceutically active compounds |
| US20030114448A1 (en) | 2001-05-31 | 2003-06-19 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| US7329662B2 (en) | 2003-10-03 | 2008-02-12 | Hoffmann-La Roche Inc. | Pyrazolo-pyridine |
| WO2005061507A1 (en) | 2003-12-16 | 2005-07-07 | Pfizer Products Inc. | Bicyclic pyrazol-4-one cannabinoid receptor ligands and uses thereof |
| MXPA06014809A (es) | 2004-06-21 | 2007-02-12 | Hoffmann La Roche | Derivados de pirazol-pirimidina. |
| WO2006030847A1 (ja) | 2004-09-17 | 2006-03-23 | Dainippon Sumitomo Pharma Co., Ltd. | 新規二環性ピラゾール誘導体 |
| DE102004054665A1 (de) | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte bi- und tricyclische Pyrazol-Derivate Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| JP4708438B2 (ja) | 2005-02-11 | 2011-06-22 | エフ.ホフマン−ラ ロシュ アーゲー | mGluR2アンタゴニストとしてのピラゾロピリミジン誘導体 |
| AU2006226669B2 (en) * | 2005-03-23 | 2011-12-08 | F. Hoffmann-La Roche Ag | Acetylenyl-pyrazolo-pvrimidine derivatives as mGluR2 antagonists |
| US7998959B2 (en) | 2006-01-12 | 2011-08-16 | Incyte Corporation | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
| US8435970B2 (en) | 2006-06-29 | 2013-05-07 | Astex Therapeutics Limited | Pharmaceutical combinations of 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea |
| PT2155747E (pt) | 2007-05-10 | 2012-12-19 | Ge Healthcare Ltd | Imidazol(1,2-a)piridinas e compostos relacionados com actividade nos receptores de canabinóides cb2 |
| EP2085390A1 (en) | 2008-01-31 | 2009-08-05 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors |
| US9446995B2 (en) | 2012-05-21 | 2016-09-20 | Illinois Institute Of Technology | Synthesis of therapeutic and diagnostic drugs centered on regioselective and stereoselective ring opening of aziridinium ions |
| CN102036953B (zh) | 2008-03-24 | 2015-05-06 | 诺华股份有限公司 | 基于芳基磺酰胺的基质金属蛋白酶抑制剂 |
| WO2009130232A1 (en) | 2008-04-24 | 2009-10-29 | Glaxo Group Limited | Pyrazolo [1, 5 -a] pyrazine derivatives as antagonists of v1b receptors |
| US20110230472A1 (en) | 2008-08-29 | 2011-09-22 | Shionogi & Co., Ltd. | Ring-fused azole derivative having pi3k-inhibiting activity |
| JP5547194B2 (ja) | 2008-09-02 | 2014-07-09 | 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. | 代謝型グルタミン酸受容体の調節因子としての3−アザビシクロ[3.1.0]ヘキシル誘導体 |
| CN102439008B (zh) | 2009-05-12 | 2015-04-29 | 杨森制药有限公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其用于治疗或预防神经和精神病症的用途 |
| 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 |
| WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
| EP2638040A1 (en) * | 2010-11-08 | 2013-09-18 | Janssen Pharmaceuticals, Inc. | RADIOLABELLED mGLuR2 PET LIGANDS |
| US8592422B2 (en) | 2010-12-17 | 2013-11-26 | Vanderbilt University | Bicyclic triazole and pyrazole lactams as allosteric modulators of mGluR5 receptors |
| GB201106817D0 (en) | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compound |
| EP2734520B1 (en) | 2011-07-19 | 2016-09-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| MX2014000648A (es) | 2011-07-19 | 2014-09-25 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y sus usos. |
| MX344308B (es) | 2011-11-03 | 2016-12-13 | Merck Sharp & Dohme | Derivados de quinolina carboxamida y quinolina carbonitrilo como moduladores alostericos negativos de mglur2, composiciones y su uso. |
| JP2013189395A (ja) | 2012-03-14 | 2013-09-26 | Dainippon Sumitomo Pharma Co Ltd | ジヒドロピロロピラジノン誘導体 |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US20130281397A1 (en) | 2012-04-19 | 2013-10-24 | Rvx Therapeutics Inc. | Treatment of diseases by epigenetic regulation |
| EP2666775A1 (en) | 2012-05-21 | 2013-11-27 | Domain Therapeutics | Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors |
| WO2013192347A1 (en) | 2012-06-20 | 2013-12-27 | Vanderbilt University | Substituted bicyclic cycloalkyl pyrazole lactam analogs as allosteric modulators of mglur5 receptors |
| WO2013192350A1 (en) | 2012-06-20 | 2013-12-27 | Vanderbilt University | Substituted bicyclic aralkyl pyrazole lactam analogs as allosteric modulators of mglur5 receptors |
| CA2876979A1 (en) | 2012-06-20 | 2013-12-27 | P. Jeffrey Conn | Substituted bicyclic alkoxy pyrazole analogs as allosteric modulators of mglur5 receptors |
| EP2870150B1 (en) | 2012-07-03 | 2019-06-19 | 3-V Biosciences, Inc. | Heterocyclic modulators of lipid synthesis |
| AR093077A1 (es) | 2012-10-23 | 2015-05-20 | Hoffmann La Roche | ANTAGONISTAS DE mGlu2/3 PARA EL TRATAMIENTO DE LOS TRASTORNOS AUTISTAS |
| 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 |
| SG11201509186TA (en) | 2013-06-27 | 2016-01-28 | Pfizer | Heteroaromatic compounds and their use as dopamine d1 ligands |
| EA034893B1 (ru) | 2013-06-27 | 2020-04-02 | Янссен Сайенсиз Айрлэнд Юси | Производные пирроло[3,2-d]пиримидина для лечения вирусных инфекций и других заболеваний |
| AU2015295301B2 (en) | 2014-08-01 | 2019-05-09 | Janssen Pharmaceutica Nv | 6,7-dihydropyrazolo[1,5-alpha]pyrazin-4(5H)-one compounds and their use as negative allosteric modulators of mGluR2 receptors |
| JOP20150177B1 (ar) | 2014-08-01 | 2021-08-17 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| RU2708391C2 (ru) | 2014-08-01 | 2019-12-06 | Янссен Фармацевтика Нв | 6,7-дигидропиразоло[1,5-а]пиразин-4(5h)-оновые соединения и их применение в качестве отрицательных аллостерических модуляторов рецепторов mglur2 |
| JO3601B1 (ar) | 2014-08-01 | 2020-07-05 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| JOP20150179B1 (ar) | 2014-08-01 | 2021-08-17 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| US10967078B2 (en) | 2014-12-03 | 2021-04-06 | Janssen Pharmaceutica Nv | Radiolabelled mGluR2 PET ligands |
| ES2727379T3 (es) | 2014-12-03 | 2019-10-15 | Janssen Pharmaceutica Nv | Compuestos de 6,7-dihidropirazolo[1,5-a]pirazin-4(5H)-ona y su uso como moduladores alostéricos negativos de receptores de mGlu2 |
| JP2016124810A (ja) * | 2014-12-26 | 2016-07-11 | 大日本住友製薬株式会社 | 新規縮合ピラゾール誘導体およびその医薬用途 |
| EP3389728B1 (en) | 2015-12-18 | 2020-08-05 | Janssen Pharmaceutica NV | Radiolabelled mglur2/3 pet ligands |
| SI3389727T1 (sl) | 2015-12-18 | 2020-10-30 | Janssen Pharmaceutica Nv | Radioaktivno označeni ligandi PET MGLUR2/3 |
-
2016
- 2016-12-16 SI SI201630916T patent/SI3389727T1/sl unknown
- 2016-12-16 WO PCT/EP2016/081542 patent/WO2017103182A1/en not_active Ceased
- 2016-12-16 PT PT168129617T patent/PT3389727T/pt unknown
- 2016-12-16 EP EP16812961.7A patent/EP3389727B1/en active Active
- 2016-12-16 HR HRP20201372TT patent/HRP20201372T1/hr unknown
- 2016-12-16 SM SM20200591T patent/SMT202000591T1/it unknown
- 2016-12-16 US US16/061,437 patent/US11033641B2/en not_active Expired - Fee Related
- 2016-12-16 HU HUE16812961A patent/HUE050665T2/hu unknown
- 2016-12-16 CA CA3003998A patent/CA3003998A1/en active Pending
- 2016-12-16 JP JP2018531628A patent/JP6927974B2/ja not_active Expired - Fee Related
- 2016-12-16 ES ES16812961T patent/ES2828976T3/es active Active
- 2016-12-16 DK DK16812961.7T patent/DK3389727T3/da active
- 2016-12-16 RS RS20201288A patent/RS60981B1/sr unknown
- 2016-12-16 AU AU2016374571A patent/AU2016374571B2/en not_active Ceased
- 2016-12-16 LT LTEP16812961.7T patent/LT3389727T/lt unknown
- 2016-12-16 PL PL16812961T patent/PL3389727T3/pl unknown
-
2020
- 2020-11-09 CY CY20201101051T patent/CY1124935T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3003998A1 (en) | 2017-06-22 |
| HRP20201372T1 (hr) | 2020-11-27 |
| JP6927974B2 (ja) | 2021-09-01 |
| WO2017103182A1 (en) | 2017-06-22 |
| EP3389727B1 (en) | 2020-08-12 |
| HUE050665T2 (hu) | 2020-12-28 |
| CY1124935T1 (el) | 2022-07-22 |
| ES2828976T3 (es) | 2021-05-28 |
| RS60981B1 (sr) | 2020-11-30 |
| US20200306389A1 (en) | 2020-10-01 |
| JP2019502700A (ja) | 2019-01-31 |
| SMT202000591T1 (it) | 2020-11-10 |
| EP3389727A1 (en) | 2018-10-24 |
| DK3389727T3 (da) | 2020-11-02 |
| PL3389727T3 (pl) | 2021-02-08 |
| AU2016374571A1 (en) | 2018-05-17 |
| PT3389727T (pt) | 2020-10-30 |
| LT3389727T (lt) | 2020-10-12 |
| AU2016374571B2 (en) | 2021-05-06 |
| US11033641B2 (en) | 2021-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| GB201507594D0 (en) | Intamac 1 | |
| GB201521134D0 (en) | Privitar case 1 | |
| IL259966B (en) | Radiolabelled mglur2/3 pet ligands | |
| LT3389727T (lt) | Radioaktyviai pažymėti mglur2/3 pet ligandai | |
| GB201513478D0 (en) | Pet hideaways | |
| AU5457P (en) | JOAe 6656 Aeonium arborium | |
| GB201521163D0 (en) | Concept 78 | |
| GB201521164D0 (en) | Concept 85 | |
| GB201521157D0 (en) | Concept 74 | |
| GB201521158D0 (en) | Concept 82 | |
| GB201521156D0 (en) | Concept 80 | |
| GB201505171D0 (en) | Concept 37 | |
| GB201505175D0 (en) | Concept 40 | |
| GB201505148D0 (en) | Concept 32 | |
| GB201505164D0 (en) | Concept 16 | |
| GB201505155D0 (en) | Concept 21 | |
| GB201505172D0 (en) | Concept 38 | |
| GB201505173D0 (en) | Concept 39 | |
| GB201505154D0 (en) | Concept 22 | |
| GB201505153D0 (en) | Concept 23 | |
| GB201505176D0 (en) | Concept 43 | |
| GB201505179D0 (en) | Concept 54 | |
| GB201505183D0 (en) | Concept 52 | |
| GB201505152D0 (en) | Concept 29 | |
| GB201505188D0 (en) | Concept 47 |