JP4554364B2 - インテグリンと選択的に結合するピペリジニル化合物 - Google Patents
インテグリンと選択的に結合するピペリジニル化合物 Download PDFInfo
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- JP4554364B2 JP4554364B2 JP2004532905A JP2004532905A JP4554364B2 JP 4554364 B2 JP4554364 B2 JP 4554364B2 JP 2004532905 A JP2004532905 A JP 2004532905A JP 2004532905 A JP2004532905 A JP 2004532905A JP 4554364 B2 JP4554364 B2 JP 4554364B2
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- Prior art keywords
- alkyl
- compound
- tetrahydro
- naphthyridin
- formula
- 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.)
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- 108010044426 integrins Proteins 0.000 title description 85
- 102000006495 integrins Human genes 0.000 title description 85
- 125000003386 piperidinyl group Chemical group 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 626
- 125000000217 alkyl group Chemical group 0.000 claims description 494
- 239000000203 mixture Substances 0.000 claims description 202
- -1 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl Chemical group 0.000 claims description 196
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 155
- 229910052739 hydrogen Inorganic materials 0.000 claims description 94
- 239000001257 hydrogen Substances 0.000 claims description 92
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 90
- 125000003545 alkoxy group Chemical group 0.000 claims description 66
- 125000001424 substituent group Chemical group 0.000 claims description 52
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 125000004043 oxo group Chemical group O=* 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
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- RBSUHEPCSZKVSP-UHFFFAOYSA-N 3-quinolin-3-yl-3-[1-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butanoyl]piperidin-4-yl]propanoic acid Chemical compound C1=CC=CC2=CC(C(C3CCN(CC3)C(=O)CCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 RBSUHEPCSZKVSP-UHFFFAOYSA-N 0.000 description 66
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
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- DNQWHMAMMCDOER-UHFFFAOYSA-N 3-pyridin-3-yl-5-[1-[4-(pyridin-2-ylamino)butanoyl]piperidin-4-yl]pentanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)CCC(CC1)CCN1C(=O)CCCNC1=CC=CC=N1 DNQWHMAMMCDOER-UHFFFAOYSA-N 0.000 description 17
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- 125000003118 aryl group Chemical group 0.000 description 15
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
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- 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 description 13
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- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 10
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Classifications
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
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- C07—ORGANIC CHEMISTRY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
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- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Rheumatology (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
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- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40423902P | 2002-08-16 | 2002-08-16 | |
| PCT/US2003/025782 WO2004020435A1 (en) | 2002-08-16 | 2003-08-15 | Piperidinyl compounds that selectively bind integrins |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005539049A JP2005539049A (ja) | 2005-12-22 |
| JP2005539049A5 JP2005539049A5 (https=) | 2006-06-29 |
| JP4554364B2 true JP4554364B2 (ja) | 2010-09-29 |
Family
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Family Applications (1)
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| JP (1) | JP4554364B2 (https=) |
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| CN (1) | CN100506815C (https=) |
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| AT (1) | ATE489378T1 (https=) |
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| CA (1) | CA2496127C (https=) |
| CR (1) | CR7692A (https=) |
| CY (1) | CY1111194T1 (https=) |
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| IL (1) | IL166534A (https=) |
| MX (1) | MXPA05001859A (https=) |
| NO (1) | NO332036B1 (https=) |
| PL (1) | PL219749B1 (https=) |
| PT (1) | PT1539739E (https=) |
| RU (1) | RU2333210C2 (https=) |
| SI (1) | SI1539739T1 (https=) |
| UA (1) | UA83467C2 (https=) |
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Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040224986A1 (en) | 2002-08-16 | 2004-11-11 | Bart De Corte | Piperidinyl targeting compounds that selectively bind integrins |
| US7351711B2 (en) | 2003-07-31 | 2008-04-01 | Janssen Pharmaceutical, N.V. | Tricyclic indanyls as integrin inhibitors |
| ES2671522T3 (es) * | 2004-04-02 | 2018-06-06 | The Regents Of The University Of California | Métodos y composiciones para tratar y prevenir una enfermedad asociada con la integrina alfa V beta 5 |
| EP1830902A2 (en) * | 2004-12-30 | 2007-09-12 | Cinvention Ag | Combination comprising an agent providing a signal, an implant material and a drug |
| CN101272808B (zh) * | 2005-01-06 | 2012-03-21 | 通用电气医疗集团股份有限公司 | 光学成像 |
| US8636995B2 (en) * | 2006-08-31 | 2014-01-28 | Cardiac Pacemakers, Inc. | Methods and devices to regulate stem cell homing |
| US8372399B2 (en) * | 2006-08-31 | 2013-02-12 | Cardiac Pacemakers, Inc. | Bispecific antibodies and agents to enhance stem cell homing |
| US20080058922A1 (en) * | 2006-08-31 | 2008-03-06 | Cardiac Pacemakers, Inc. | Methods and devices employing vap-1 inhibitors |
| PT2178858E (pt) | 2007-08-02 | 2012-02-24 | Recordati Ireland Ltd | Novos compostos heterocíclicos como antagonistas de mglu5 |
| ES2474165T3 (es) | 2007-10-30 | 2014-07-08 | Janssen Pharmaceutica N.V. | Proceso enantioselectivo para preparar un ácido alcanoico sustituido |
| ES2457822T3 (es) * | 2007-11-08 | 2014-04-29 | The General Hospital Corporation | Procedimientos y composiciones de tratamiento de enfermedades proteinúricas |
| CA2767409C (en) | 2009-07-24 | 2018-10-30 | The Regents Of The University Of California | Methods and compositions for treating and preventing disease associated with .alpha.v.beta.5 integrin |
| PL3050878T3 (pl) | 2013-09-24 | 2022-01-24 | Fujifilm Corporation | Zawierający atom azotu związek lub jego sól, lub ich kompleks z metalem |
| JP2019530678A (ja) | 2016-09-18 | 2019-10-24 | エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド | Ｙａｐ１のｏｃｔ４との相互作用を標的とするｙａｐ１阻害剤 |
| MX2019005234A (es) * | 2016-11-08 | 2019-08-12 | Squibb Bristol Myers Co | Amidas y aminas de azol como inhibidores de integrina alfa v. |
| SI3538528T1 (sl) * | 2016-11-08 | 2021-03-31 | Bristol-Myers Squibb Company | Pirol amidi kot alfa v integrin inhibitorji |
| MA52117A (fr) * | 2017-02-28 | 2022-04-06 | Morphic Therapeutic Inc | Inhibiteurs de l'intégrine (alpha-v) (bêta-6) |
| MA47697A (fr) | 2017-02-28 | 2020-01-08 | Morphic Therapeutic Inc | Inhibiteurs de l'(alpha-v)(bêta-6) intégrine |
| BR112020018642A2 (pt) | 2018-03-14 | 2020-12-29 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Composto da fórmula i, composição farmacêutica, método de tratamento de câncer em um sujeito em necessidade, método de eliminação de uma célula tumoral em um sujeito |
| EP4086254B1 (en) | 2018-08-29 | 2024-12-18 | Morphic Therapeutic, Inc. | Integrin inhibitors |
| FI3844162T3 (fi) | 2018-08-29 | 2025-03-27 | Morphic Therapeutic Inc | Alfa v beeta6 -integriinin estäjiä |
| WO2020047208A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| WO2025067433A1 (zh) * | 2023-09-28 | 2025-04-03 | 云合智药（苏州）生物科技有限公司 | 靶向整合素的化合物及其在RNAi剂中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN148482B (https=) * | 1977-06-03 | 1981-03-07 | Pfizer | |
| EP1306095A3 (en) * | 1992-03-05 | 2003-06-25 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
| US5474765A (en) * | 1992-03-23 | 1995-12-12 | Ut Sw Medical Ctr At Dallas | Preparation and use of steroid-polyanionic polymer-based conjugates targeted to vascular endothelial cells |
| US5902795A (en) * | 1992-06-16 | 1999-05-11 | Trustees Of Tufts College | Oligosaccharides reactive with hyaluronan-binding protein and their methods of use |
| US5340798A (en) * | 1992-10-14 | 1994-08-23 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| US5700801A (en) * | 1994-12-23 | 1997-12-23 | Karl Thomae, Gmbh | Piperazine derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| DE19516483A1 (de) * | 1995-05-05 | 1996-11-07 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| DE19613933A1 (de) * | 1996-04-06 | 1997-10-09 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
| US5919792A (en) * | 1996-10-30 | 1999-07-06 | Merck & Co., Inc. | Integrin antagonists |
| CA2315232A1 (en) * | 1997-12-17 | 1999-06-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6211191B1 (en) * | 1997-12-17 | 2001-04-03 | Merck & Co., Inc. | Integrin receptor antagonists |
| CA2333647A1 (en) * | 1998-06-29 | 2000-01-06 | Dupont Pharmaceuticals Company | Cyclic carbamates and isoxazolidines as iib/iiia antagonists |
| EP1179541B1 (en) * | 1999-04-28 | 2004-06-16 | Board Of Regents, The University Of Texas System | Compositions and methods for cancer treatment by selectively inhibiting VEGF |
| US6776796B2 (en) * | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
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2003
- 2003-08-15 DK DK03791686.3T patent/DK1539739T3/da active
- 2003-08-15 CA CA2496127A patent/CA2496127C/en not_active Expired - Fee Related
- 2003-08-15 WO PCT/US2003/025782 patent/WO2004020435A1/en not_active Ceased
- 2003-08-15 BR BR0313534-9A patent/BR0313534A/pt not_active IP Right Cessation
- 2003-08-15 UA UAA200502396A patent/UA83467C2/uk unknown
- 2003-08-15 KR KR1020057001657A patent/KR20050031464A/ko not_active Ceased
- 2003-08-15 AU AU2003259891A patent/AU2003259891A1/en not_active Abandoned
- 2003-08-15 AR ARP030102976A patent/AR041010A1/es unknown
- 2003-08-15 SI SI200331951T patent/SI1539739T1/sl unknown
- 2003-08-15 US US10/641,964 patent/US20040077684A1/en not_active Abandoned
- 2003-08-15 EP EP03791686A patent/EP1539739B1/en not_active Expired - Lifetime
- 2003-08-15 DE DE60335118T patent/DE60335118D1/de not_active Expired - Lifetime
- 2003-08-15 JP JP2004532905A patent/JP4554364B2/ja not_active Expired - Fee Related
- 2003-08-15 MX MXPA05001859A patent/MXPA05001859A/es active IP Right Grant
- 2003-08-15 AT AT03791686T patent/ATE489378T1/de active
- 2003-08-15 CN CNB038240904A patent/CN100506815C/zh not_active Expired - Fee Related
- 2003-08-15 ES ES03791686T patent/ES2355139T3/es not_active Expired - Lifetime
- 2003-08-15 PL PL375562A patent/PL219749B1/pl unknown
- 2003-08-15 PT PT03791686T patent/PT1539739E/pt unknown
- 2003-08-15 RU RU2005104115/04A patent/RU2333210C2/ru not_active IP Right Cessation
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2005
- 2005-01-27 IL IL166534A patent/IL166534A/en not_active IP Right Cessation
- 2005-02-15 CR CR7692A patent/CR7692A/es unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| IL166534A (en) | 2012-05-31 |
| CN100506815C (zh) | 2009-07-01 |
| CN1688572A (zh) | 2005-10-26 |
| NO20051273L (no) | 2005-05-10 |
| AU2010236002B2 (en) | 2012-05-03 |
| CA2496127C (en) | 2012-05-29 |
| AR041010A1 (es) | 2005-04-27 |
| US20040077684A1 (en) | 2004-04-22 |
| ES2355139T3 (es) | 2011-03-23 |
| SI1539739T1 (sl) | 2011-04-29 |
| RU2333210C2 (ru) | 2008-09-10 |
| MXPA05001859A (es) | 2005-06-03 |
| EP1539739A1 (en) | 2005-06-15 |
| NO332036B1 (no) | 2012-06-04 |
| CR7692A (es) | 2009-01-14 |
| DE60335118D1 (de) | 2011-01-05 |
| AU2010236002A1 (en) | 2010-11-11 |
| ATE489378T1 (de) | 2010-12-15 |
| BR0313534A (pt) | 2005-07-12 |
| RU2005104115A (ru) | 2005-08-27 |
| UA83467C2 (uk) | 2008-07-25 |
| CY1111194T1 (el) | 2015-06-11 |
| JP2005539049A (ja) | 2005-12-22 |
| PT1539739E (pt) | 2011-01-05 |
| IL166534A0 (en) | 2006-01-15 |
| WO2004020435A1 (en) | 2004-03-11 |
| KR20050031464A (ko) | 2005-04-06 |
| EP1539739B1 (en) | 2010-11-24 |
| CA2496127A1 (en) | 2005-02-16 |
| AU2003259891A1 (en) | 2004-03-19 |
| PL375562A1 (en) | 2005-11-28 |
| PL219749B1 (pl) | 2015-07-31 |
| DK1539739T3 (da) | 2011-03-07 |
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