CA2475633C - Heteroaryl compounds useful as inhibitors of gsk-3 - Google Patents
Heteroaryl compounds useful as inhibitors of gsk-3 Download PDFInfo
- Publication number
- CA2475633C CA2475633C CA2475633A CA2475633A CA2475633C CA 2475633 C CA2475633 C CA 2475633C CA 2475633 A CA2475633 A CA 2475633A CA 2475633 A CA2475633 A CA 2475633A CA 2475633 C CA2475633 C CA 2475633C
- Authority
- CA
- Canada
- Prior art keywords
- benzoimidazol
- furazan
- ring
- aliphatic
- optionally substituted
- 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.)
- Expired - Fee Related
Links
- 125000001072 heteroaryl group Chemical group 0.000 title claims description 18
- 239000003112 inhibitor Substances 0.000 title abstract description 24
- 101150090422 gsk-3 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 136
- 239000000203 mixture Substances 0.000 claims abstract description 129
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 101
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 78
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 43
- 229910052717 sulfur Chemical group 0.000 claims abstract description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 37
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 37
- 125000001424 substituent group Chemical group 0.000 claims abstract description 37
- 239000011593 sulfur Chemical group 0.000 claims abstract description 37
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000001301 oxygen Chemical group 0.000 claims abstract description 36
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims abstract description 31
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 206010052779 Transplant rejections Diseases 0.000 claims abstract description 7
- 208000035475 disorder Diseases 0.000 claims abstract description 7
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 claims abstract 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 80
- -1 1,2-ethylenedioxy Chemical group 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 23
- 125000001118 alkylidene group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 108010002481 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proteins 0.000 claims description 11
- 102000036243 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Human genes 0.000 claims description 11
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 206010020751 Hypersensitivity Diseases 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
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- 201000000980 schizophrenia Diseases 0.000 claims description 10
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
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- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 6
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- QEPDSNAEMKSMGN-UHFFFAOYSA-N chembl1329127 Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1 QEPDSNAEMKSMGN-UHFFFAOYSA-N 0.000 claims description 6
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- 125000004423 acyloxy group Chemical group 0.000 claims description 5
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- 125000003838 furazanyl group Chemical group 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 3
- GLQIZLCZHSQBLY-UHFFFAOYSA-N 2-(1h-benzimidazol-2-yl)-4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1C1=NC2=CC=CC=C2N1 GLQIZLCZHSQBLY-UHFFFAOYSA-N 0.000 claims 2
- JMSNVUTXNCLSSL-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2,4-difluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=C(F)C=C1F JMSNVUTXNCLSSL-UHFFFAOYSA-N 0.000 claims 2
- OIIBRYKPFULYFU-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1C2=CC=CC=C2N=C1C1=NON=C1N OIIBRYKPFULYFU-UHFFFAOYSA-N 0.000 claims 2
- MWPXMWVHOXXWCY-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2-phenylphenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=CC=C1C1=CC=CC=C1 MWPXMWVHOXXWCY-UHFFFAOYSA-N 0.000 claims 2
- RKDKILJBYDCMPH-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3,4-difluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=C(F)C(F)=C1 RKDKILJBYDCMPH-UHFFFAOYSA-N 0.000 claims 2
- CLAATNFGGLOUTN-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3,4-dimethoxyphenyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CN1C2=CC=CC=C2N=C1C1=NON=C1N CLAATNFGGLOUTN-UHFFFAOYSA-N 0.000 claims 2
- IBQVTCXZQBZBDN-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3-fluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=CC(F)=C1 IBQVTCXZQBZBDN-UHFFFAOYSA-N 0.000 claims 2
- DLHZNLYFGBAMAP-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-tert-butylacetamide Chemical compound N=1C2=CC=CC=C2N(CC(=O)NC(C)(C)C)C=1C1=NON=C1N DLHZNLYFGBAMAP-UHFFFAOYSA-N 0.000 claims 2
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- PZFLXZUSYPMQHT-UHFFFAOYSA-N 2-[[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]methyl]benzonitrile Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC1=CC=CC=C1C#N PZFLXZUSYPMQHT-UHFFFAOYSA-N 0.000 claims 2
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- ZIHIDNWPEZFEMR-UHFFFAOYSA-N 4-(1-methylbenzimidazol-2-yl)-1,2,5-oxadiazol-3-amine Chemical compound N=1C2=CC=CC=C2N(C)C=1C1=NON=C1N ZIHIDNWPEZFEMR-UHFFFAOYSA-N 0.000 claims 2
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- KNJOGMJHNSVZCC-UHFFFAOYSA-N 4-[1-(2h-tetrazol-5-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC1=NNN=N1 KNJOGMJHNSVZCC-UHFFFAOYSA-N 0.000 claims 2
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Landscapes
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| US35484302P | 2002-02-06 | 2002-02-06 | |
| US60/354,843 | 2002-02-06 | ||
| PCT/US2003/003655 WO2003066629A2 (en) | 2002-02-06 | 2003-02-06 | Heteroaryl compounds useful as inhibitors of gsk-3 |
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| CA2475633A1 CA2475633A1 (en) | 2003-08-14 |
| CA2475633C true CA2475633C (en) | 2013-04-02 |
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| GB0206860D0 (en) * | 2002-03-22 | 2002-05-01 | Glaxo Group Ltd | Compounds |
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| US7459454B2 (en) | 2003-03-21 | 2008-12-02 | Smithkline Beecham Corporation | Aminopyrazine derivatives and compositions |
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| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| AR045134A1 (es) * | 2003-07-29 | 2005-10-19 | Smithkline Beecham Plc | Compuesto de 1h - imidazo [4,5-c] piridin-ilo, composicion farmaceutica que lo comprende, proceso para prepararla, su uso para preparar dicha composicion farmaceutica, combinacion farmaceutica, uso de la combinacion farmaceutica para la preparacion de un medicamento, procedimientos para preparar dic |
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| WO2005034866A2 (en) * | 2003-10-06 | 2005-04-21 | Glaxo Group Limited | Preparation of 1, 6, 7- trisubstituted azabenzimidazoles as kinase inhibitors |
| DE102004010207A1 (de) | 2004-03-02 | 2005-09-15 | Aventis Pharma S.A. | Neue 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate |
| DE102004010194A1 (de) * | 2004-03-02 | 2005-10-13 | Aventis Pharma Deutschland Gmbh | 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate, ihre Herstellung und Verwendung in Arzneimitteln |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| WO2006019831A1 (en) | 2004-07-14 | 2006-02-23 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| WO2006019832A1 (en) | 2004-07-22 | 2006-02-23 | Ptc Therapeutics, Inc. | Thienopyridines for treating hepatitis c |
| US7674907B2 (en) * | 2004-07-23 | 2010-03-09 | Amgen Inc. | Furanopyridine derivatives and methods of use |
| US8771754B2 (en) * | 2004-09-17 | 2014-07-08 | Vanderbilt University | Use of GSK3 inhibitors in combination with radiation therapies |
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| US20060204980A1 (en) * | 2004-12-28 | 2006-09-14 | Altieri Dario C | Colorectal cancer therapies |
| MX2007008008A (es) | 2004-12-30 | 2007-11-12 | Astex Therapeutics Ltd | Compuestos de pirazol que modulan la actividad de las cinasas cdk, gsk y aurora. |
| JP2008526721A (ja) | 2004-12-30 | 2008-07-24 | アステックス、セラピューティックス、リミテッド | Ｃｄｋ、ｇｓｋ及びオーロラキナーゼの活性を調節するチアゾールおよびイソチアゾール誘導体 |
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| ZA200709817B (en) | 2005-04-21 | 2009-02-25 | Serono Lab | 2,3 substituted pyrazine sulfonmides as inhibitors of CRTH2 |
| CA2609980C (en) | 2005-05-27 | 2015-10-13 | Queen's University At Kingston | Treatment of protein folding disorders |
| DE102005025225A1 (de) | 2005-06-01 | 2006-12-07 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung von 2-(2-Amino-pyrimidin-4-yl)-1H-indol-5-carbonsäure-derivaten |
| US7855289B2 (en) * | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8093401B2 (en) | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
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| US7625890B2 (en) | 2005-11-10 | 2009-12-01 | Smithkline Beecham Corp. | Substituted imidazo[4,5-c]pyridine compounds as Akt inhibitors |
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| WO2008130368A2 (en) * | 2006-06-23 | 2008-10-30 | Paratek Pharmaceuticals, Inc. | Transcription factor modulating compounds and methods of use thereof |
| CN101479249B (zh) | 2006-06-29 | 2012-10-10 | 霍夫曼-拉罗奇有限公司 | 苯并咪唑衍生物、其制备方法、它们作为fxr激动剂的用途及含有它们的药物制剂 |
| JP5523829B2 (ja) | 2006-06-29 | 2014-06-18 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
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| CA2668744C (en) * | 2006-11-17 | 2015-09-15 | Queen's University At Kingston | Compounds and methods for treating protein folding disorders |
| SG144809A1 (en) | 2007-01-11 | 2008-08-28 | Millipore U K Ltd | Benzimidazole compounds and their use as chromatographic ligands |
| UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| CL2008001822A1 (es) | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
| GB0713259D0 (en) * | 2007-07-09 | 2007-08-15 | Astrazeneca Ab | Pyrazine derivatives 954 |
| WO2009024825A1 (en) * | 2007-08-21 | 2009-02-26 | Astrazeneca Ab | 2-pyrazinylbenzimidazole derivatives as receptor tyrosine kinase inhibitors |
| CN102083799B (zh) | 2007-08-27 | 2013-10-16 | 霍夫曼-拉罗奇有限公司 | 用作fxr激动剂的苯并咪唑衍生物 |
| JP2011500778A (ja) | 2007-10-25 | 2011-01-06 | アストラゼネカ・アクチエボラーグ | ピリジン及びピラジン誘導体−０８３ |
| WO2009058348A1 (en) * | 2007-11-01 | 2009-05-07 | Sirtris Pharmaceuticals, Inc. | Amide derivatives as sirtuin modulators |
| MX2010005186A (es) * | 2007-11-08 | 2010-05-27 | Sirtris Pharmaceuticals Inc | Tiazolopiridinas solubilizadas. |
| WO2009062874A2 (en) * | 2007-11-15 | 2009-05-22 | F. Hoffmann-La Roche Ag | Benzimidazole derivatives and their use as fxr agonists |
| US7816540B2 (en) * | 2007-12-21 | 2010-10-19 | Hoffmann-La Roche Inc. | Carboxyl- or hydroxyl-substituted benzimidazole derivatives |
| AU2009276548A1 (en) * | 2008-07-30 | 2010-02-04 | Oncotherapy Science, Inc. | Benzoimidazole derivatives and glycogen synthase kinase-3 beta inhibitors containing the same |
| CA2743134A1 (en) | 2008-11-10 | 2010-05-14 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| BRPI0922435A2 (pt) | 2008-12-19 | 2018-09-11 | Sirtris Pharmaceuticals Inc | "composto de tiazolopiridina moduladores de sirtuina, composição farmacêutica compreendendo o mesmo e seu uso." |
| ES2921576T3 (es) | 2008-12-19 | 2022-08-29 | Vertex Pharma | Compuestos útiles como inhibidores de la quinasa ATR |
| CN102405047B (zh) * | 2009-01-30 | 2014-07-09 | 葛兰素史密斯克莱有限责任公司 | 结晶型的n-{(1s)-2-氨基-1-[(3-氟苯基)甲基]乙基}-5-氯-4-(4-氯-1-甲基-1h-吡唑-5-基)-2-噻吩甲酰胺盐酸盐 |
| EP2251010A1 (en) * | 2009-05-08 | 2010-11-17 | Sygnis Bioscience GmbH & Co. KG | Use of thiabendazole and derivatives thereof for the therapy of neurological conditions |
| EP2430016B1 (en) | 2009-05-13 | 2020-04-01 | University Of Virginia Patent Foundation | Inhibitors of inv(16) leukemia |
| DE102009033208A1 (de) * | 2009-07-15 | 2011-01-20 | Merck Patent Gmbh | Aminopyridinderivate |
| NZ597376A (en) * | 2009-07-27 | 2014-01-31 | Basilea Pharmaceutica Ag | Furazanobenzimidazoles as prodrugs to treat neoplastic or autoimmune diseases |
| WO2011022721A1 (en) * | 2009-08-21 | 2011-02-24 | Microbiotix, Inc | Inhibitors of botulinum neurotoxins |
| KR20120115252A (ko) | 2009-11-06 | 2012-10-17 | 벤더르빌트 유니버시티 | Ｍｇｌｕｒ4 알로스테릭 강화제로서 아릴 및 헤테로아릴 설폰, 조성물 및 신경 기능이상을 치료하는 방법 |
| US9062008B2 (en) | 2010-05-12 | 2015-06-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US9334244B2 (en) | 2010-05-12 | 2016-05-10 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8962631B2 (en) | 2010-05-12 | 2015-02-24 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| CA2798760A1 (en) | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | 2-aminopyridine derivatives useful as inhibitors of atr kinase |
| EP2568984A1 (en) | 2010-05-12 | 2013-03-20 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| NZ603477A (en) | 2010-05-12 | 2014-09-26 | Vertex Pharma | Compounds useful as inhibitors of atr kinase |
| MX2013000103A (es) | 2010-06-23 | 2013-06-13 | Vertex Pharma | Derivados de pirrolo-pirazina utiles como inhibidores de cinasa art. |
| MX2013011450A (es) | 2011-04-05 | 2014-02-03 | Vertex Pharma | Compuestos de aminopirazina utiles como inhibidores de la cinasa ataxia telangiectasia mutada y rad3 relacionados (atr). |
| US8822469B2 (en) | 2011-06-22 | 2014-09-02 | Vertex Pharmaceuticals Incorporated | Pyrrolo[2,3-B]pyrazines useful as inhibitors of ATR kinase |
| EP2723747A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| US9309250B2 (en) | 2011-06-22 | 2016-04-12 | Vertex Pharmaceuticals Incorporated | Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors |
| EP2554662A1 (en) | 2011-08-05 | 2013-02-06 | M Maria Pia Cosma | Methods of treatment of retinal degeneration diseases |
| US9351973B2 (en) | 2011-09-22 | 2016-05-31 | Merck Sharp & Dohme Corp. | Pyrazolopyridyl compounds as aldosterone synthase inhibitors |
| EP2757882B1 (en) | 2011-09-22 | 2020-11-04 | Merck Sharp & Dohme Corp. | Imidazopyridyl compounds as aldosterone synthase inhibitors |
| EP2757883B1 (en) | 2011-09-22 | 2021-01-13 | Merck Sharp & Dohme Corp. | Triazolopyridyl compounds as aldosterone synthase inhibitors |
| WO2013049720A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013049722A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| CN108685922A (zh) | 2011-09-30 | 2018-10-23 | 沃泰克斯药物股份有限公司 | 用atr抑制剂治疗胰腺癌和非小细胞肺癌 |
| US8765751B2 (en) | 2011-09-30 | 2014-07-01 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| CN106496173A (zh) | 2011-09-30 | 2017-03-15 | 沃泰克斯药物股份有限公司 | 用于制备可用作atr激酶抑制剂的化合物的方法 |
| US8841337B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8846918B2 (en) | 2011-11-09 | 2014-09-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP2015502925A (ja) | 2011-11-09 | 2015-01-29 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用なピラジン化合物 |
| US8846917B2 (en) | 2011-11-09 | 2014-09-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8841450B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| CN108478577A (zh) | 2012-04-05 | 2018-09-04 | 沃泰克斯药物股份有限公司 | 可用作atr激酶抑制剂的化合物及其组合疗法 |
| MX371331B (es) | 2012-04-24 | 2020-01-27 | Vertex Pharma | Inhibidores de la proteina cinasa dependiente de acido desoxirribonucleico(adn-pk). |
| DK2904406T3 (en) | 2012-10-04 | 2018-06-18 | Vertex Pharma | METHOD OF DETERMINING THE ATR INHIBITION, INCREASED DNA DAMAGE |
| CA2886117C (en) | 2012-10-05 | 2022-05-31 | Merck Sharp & Dohme Corp. | Indoline compounds and their use as aldosterone synthase inhibitors |
| EP2909202A1 (en) | 2012-10-16 | 2015-08-26 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| CA2880326A1 (en) * | 2012-10-26 | 2014-05-01 | F. Hoffmann-La Roche Ag | 3,4-disubstituted 1 h-pyrazole and 4,5-disubstituted thiazole inhibitors of syk cap |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| ME03336B (me) | 2013-03-12 | 2019-10-20 | Vertex Pharma | Inhibitori dnk-pk |
| WO2014143240A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Fused pyrazolopyrimidine derivatives useful as inhibitors of atr kinase |
| JP6408569B2 (ja) | 2013-10-17 | 2018-10-17 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ｄｎａ−ｐｋ阻害剤としての（ｓ）−ｎ−メチル−８−（１−（（２’−メチル−［４，５’−ビピリミジン］−６−イル）アミノ）プロパン−２−イル）キノリン−４−カルボキサミドおよびその重水素化誘導体の共結晶 |
| PT3077397T (pt) | 2013-12-06 | 2020-01-22 | Vertex Pharma | Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| US10294243B2 (en) | 2014-06-05 | 2019-05-21 | Bayer Cropscience Aktiengesellschaft | Bicyclic compounds as pesticides |
| MX373102B (es) | 2014-06-05 | 2020-04-17 | Vertex Pharma | Derivados radiomarcados de un compuesto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]-pirazolo[1,5-a]pirimidin-3-carboxamida útil como inhibidor de ataxia telangiectasia mutada y rad3 relacionado (atr) cinasa, preparación de tal compuesto y diferentes formas sólidas del mismo. |
| SG11201610500WA (en) | 2014-06-17 | 2017-01-27 | Vertex Pharma | Method for treating cancer using a combination of chk1 and atr inhibitors |
| BR112017013465A2 (pt) | 2014-12-24 | 2018-03-06 | Lg Chem, Ltd | derivado de biarila, e, composição farmacêutica. |
| AU2016331955B2 (en) | 2015-09-30 | 2022-07-21 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors |
| EP3231434A1 (en) | 2016-04-14 | 2017-10-18 | Fundacio Centre de Regulacio Genomica | Method of treatment of parkinsonism |
| WO2017216706A1 (en) | 2016-06-14 | 2017-12-21 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
| EP3518931A4 (en) | 2016-09-27 | 2020-05-13 | Vertex Pharmaceuticals Incorporated | METHOD FOR TREATING CANCER WITH A COMBINATION OF DNA-DAMAGING SUBSTANCES AND DNA-PK INHIBITORS |
| MX388196B (es) | 2017-04-26 | 2025-03-19 | Basilea Pharm Int Ag | Procesos para la preparacion de furazanobencimidazoles y formas cristalinas de estos. |
| US11331313B2 (en) | 2017-05-22 | 2022-05-17 | Whitehead Institute For Biomedical Research | KCC2 expression enhancing compounds and uses thereof |
| CN109265451B (zh) * | 2018-10-09 | 2022-07-15 | 中国药科大学 | 丁酰胆碱酯酶选择性抑制剂及其制备方法与用途 |
| EP3920885A1 (en) | 2019-02-08 | 2021-12-15 | Frequency Therapeutics, Inc. | Valproic acid compounds and wnt agonists for treating ear disorders |
| CN111454254B (zh) * | 2020-04-26 | 2023-06-02 | 云白药征武科技(上海)有限公司 | 一种具有含氟取代基的苯并咪唑衍生物的制备及其应用 |
| CN111423429A (zh) * | 2020-05-19 | 2020-07-17 | 江西科技师范大学 | 苯并咪唑联呋咱类系列化合物及其合成方法 |
| CN112920178A (zh) * | 2021-01-29 | 2021-06-08 | 中国药科大学 | 具有苯并咪唑结构的化合物及其制备方法与用途 |
| CN120530093A (zh) * | 2023-01-20 | 2025-08-22 | 北京炎明生物科技有限公司 | 新的alpk1抑制剂 |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3133081A (en) * | 1964-05-12 | J-aminoindazole derivatives | ||
| US3935183A (en) * | 1970-01-26 | 1976-01-27 | Imperial Chemical Industries Limited | Indazole-azo phenyl compounds |
| BE754242A (fr) * | 1970-07-15 | 1971-02-01 | Geigy Ag J R | Diamino-s-triazines et dinitro-s-triazines |
| US3998951A (en) * | 1974-03-13 | 1976-12-21 | Fmc Corporation | Substituted 2-arylquinazolines as fungicides |
| DE2458965C3 (de) * | 1974-12-13 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | 3-Amino-indazol-N-carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie sie enthaltende Arzneimittel |
| DOP1981004033A (es) * | 1980-12-23 | 1990-12-29 | Ciba Geigy Ag | Procedimiento para proteger plantas de cultivo de la accion fitotoxica de herbicidas. |
| SE8102194L (sv) * | 1981-04-06 | 1982-10-07 | Pharmacia Ab | Terapeutiskt aktiv organisk forening och farmaceutisk beredning innehallande denna |
| SE8102193L (sv) * | 1981-04-06 | 1982-10-07 | Pharmacia Ab | Terapeutiskt aktiv organisk forening och dess anvendning |
| JPS58124773A (ja) * | 1982-01-20 | 1983-07-25 | Mitsui Toatsu Chem Inc | ５−メチルチオピリミジン誘導体とその製造法と農園芸用殺菌剤 |
| US5166170A (en) * | 1989-07-03 | 1992-11-24 | Hoechst-Roussel Pharmaceuticals Incorporated | 2-(aminoaryl) indoles and indolines as topical antiinflammatory agents for the treatment of skin disorders |
| US5710158A (en) * | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5496826A (en) * | 1994-09-02 | 1996-03-05 | Bristol-Myers Squibb Company | Pharmaceutical methods of using heterocyclic derivatives of N-phenylamides |
| WO1996014843A2 (en) * | 1994-11-10 | 1996-05-23 | Cor Therapeutics, Inc. | Pharmaceutical pyrazole compositions useful as inhibitors of protein kinases |
| IL117659A (en) * | 1995-04-13 | 2000-12-06 | Dainippon Pharmaceutical Co | Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same |
| AU6966696A (en) * | 1995-10-05 | 1997-04-28 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
| US6716575B2 (en) * | 1995-12-18 | 2004-04-06 | Sugen, Inc. | Diagnosis and treatment of AUR1 and/or AUR2 related disorders |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| US6267952B1 (en) * | 1998-01-09 | 2001-07-31 | Geltex Pharmaceuticals, Inc. | Lipase inhibiting polymers |
| EA200000840A1 (ru) * | 1998-02-17 | 2001-02-26 | Туларик, Инк. | Антивирусные производные пиримидина |
| WO1999065897A1 (en) | 1998-06-19 | 1999-12-23 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| EP1105394A1 (en) * | 1998-08-21 | 2001-06-13 | Du Pont Pharmaceuticals Company | ISOXAZOLO 4,5-d]PYRIMIDINES AS CRF ANTAGONISTS |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| US6130333A (en) * | 1998-11-27 | 2000-10-10 | Monsanto Company | Bicyclic imidazolyl derivatives as phosphodiesterase inhibitors, pharmaceutical compositions and method of use |
| GB9828640D0 (en) | 1998-12-23 | 1999-02-17 | Smithkline Beecham Plc | Novel method and compounds |
| GB9828511D0 (en) * | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| DE19920936A1 (de) * | 1999-05-07 | 2000-11-09 | Basf Ag | Heterozyklisch substituierte Benzimidazole, deren Herstellung und Anwendung |
| GB9914258D0 (en) * | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| DK1194425T3 (da) * | 1999-06-23 | 2005-11-21 | Aventis Pharma Gmbh | Substituerede benzimidazoler |
| US20020065270A1 (en) * | 1999-12-28 | 2002-05-30 | Moriarty Kevin Joseph | N-heterocyclic inhibitors of TNF-alpha expression |
| KR20010111298A (ko) * | 2000-02-05 | 2001-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | Ｅｒｋ의 억제제로서 유용한 피라졸 조성물 |
| AU3704101A (en) * | 2000-02-17 | 2001-08-27 | Amgen Inc | Kinase inhibitors |
| GB0004887D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| EP1136099A1 (en) * | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-(Indolylalkylamino)pyrimidone derivatives as GSK3beta inhibitors |
| IL153246A0 (en) * | 2000-06-28 | 2003-07-06 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
| US6610677B2 (en) * | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| WO2002022605A1 (en) * | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6613776B2 (en) * | 2000-09-15 | 2003-09-02 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US7473691B2 (en) * | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6660731B2 (en) * | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| EP1317453B1 (en) * | 2000-09-15 | 2006-08-09 | Vertex Pharmaceuticals Incorporated | Isoxazoles and their use as inhibitors of erk |
| DE10061863A1 (de) * | 2000-12-12 | 2002-06-13 | Basf Ag | Verfahren zur Herstellung von Triethylendiamin (TEDA) |
| US6716851B2 (en) * | 2000-12-12 | 2004-04-06 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof |
| AU2002222293A1 (en) * | 2000-12-19 | 2002-07-01 | Smithkline Beecham P.L.C. | Pyrazolo(3,4-c)pyridines as gsk-3 inhibitors |
| US6989385B2 (en) * | 2000-12-21 | 2006-01-24 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| MY130778A (en) * | 2001-02-09 | 2007-07-31 | Vertex Pharma | Heterocyclic inhibitiors of erk2 and uses thereof |
| CA2441733A1 (en) * | 2001-03-29 | 2002-10-10 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| AU2002338642A1 (en) * | 2001-04-13 | 2002-10-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| EP1383771A1 (en) * | 2001-04-20 | 2004-01-28 | Vertex Pharmaceuticals Incorporated | 9-deazaguanine derivatives as inhibitors of gsk-3 |
| CA2444882A1 (en) * | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of gsk-3 and crystal structures of gsk-3.beta. protein and protein complexes |
| WO2002092573A2 (en) * | 2001-05-16 | 2002-11-21 | Vertex Pharmaceuticals Incorporated | Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases |
| CA2450769A1 (en) * | 2001-06-15 | 2002-12-27 | Vertex Pharmaceuticals Incorporated | 5-(2-aminopyrimidin-4-yl) benzisoxazoles as protein kinase inhibitors |
| ATE337312T1 (de) * | 2001-07-03 | 2006-09-15 | Vertex Pharma | Isoxazolyl-pyrimidines als inhibitoren von src- und lck-protein-kinasen |
| BR0213562A (pt) * | 2001-10-26 | 2004-08-31 | Aventis Pharma Inc | Benzimidazóis e análogos e seu uso como inibidores de cinases de proteìna |
| ATE466581T1 (de) * | 2001-12-07 | 2010-05-15 | Vertex Pharma | Verbindungen auf pyrimidin-basis als gsk-3-hemmer |
| US6846928B2 (en) * | 2002-03-15 | 2005-01-25 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| US20040009981A1 (en) * | 2002-03-15 | 2004-01-15 | David Bebbington | Compositions useful as inhibitors of protein kinases |
| EP1485381B8 (en) * | 2002-03-15 | 2010-05-12 | Vertex Pharmaceuticals Incorporated | Azolylaminoazine as inhibitors of protein kinases |
| DE60332433D1 (de) * | 2002-03-15 | 2010-06-17 | Vertex Pharma | Azolylaminoazine als proteinkinasehemmer |
| US20030207873A1 (en) * | 2002-04-10 | 2003-11-06 | Edmund Harrington | Inhibitors of Src and other protein kinases |
| US7304061B2 (en) * | 2002-04-26 | 2007-12-04 | Vertex Pharmaceuticals Incorporated | Heterocyclic inhibitors of ERK2 and uses thereof |
| MY141867A (en) * | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| US7361665B2 (en) * | 2002-07-09 | 2008-04-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-Jun N-terminal kinases (JNK) and other protein kinases |
| DK1636215T3 (da) * | 2003-05-23 | 2008-06-02 | Basilea Pharmaceutica Ag | Furazanobenzimidazoler |
-
2003
- 2003-02-06 WO PCT/US2003/003655 patent/WO2003066629A2/en not_active Ceased
- 2003-02-06 US US10/360,535 patent/US20040034037A1/en not_active Abandoned
- 2003-02-06 ES ES10180554.7T patent/ES2437391T3/es not_active Expired - Lifetime
- 2003-02-06 RU RU2004126671/04A patent/RU2004126671A/ru not_active Application Discontinuation
- 2003-02-06 EP EP10180554.7A patent/EP2322521B1/en not_active Expired - Lifetime
- 2003-02-06 EP EP03710903A patent/EP1472245A2/en not_active Withdrawn
- 2003-02-06 CA CA2475633A patent/CA2475633C/en not_active Expired - Fee Related
- 2003-02-06 PL PL03372198A patent/PL372198A1/xx not_active Application Discontinuation
- 2003-02-06 MX MXPA04007697A patent/MXPA04007697A/es not_active Application Discontinuation
- 2003-02-06 KR KR10-2004-7012258A patent/KR20040084896A/ko not_active Withdrawn
- 2003-02-06 JP JP2003566002A patent/JP4656838B2/ja not_active Expired - Fee Related
- 2003-02-06 AU AU2003215087A patent/AU2003215087B2/en not_active Ceased
- 2003-02-06 SG SG200605228-6A patent/SG159380A1/en unknown
-
2004
- 2004-09-06 NO NO20043726A patent/NO20043726L/no unknown
-
2007
- 2007-07-12 US US11/776,756 patent/US20070270420A1/en not_active Abandoned
-
2010
- 2010-02-26 JP JP2010043557A patent/JP2010132697A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PL372198A1 (en) | 2005-07-11 |
| MXPA04007697A (es) | 2004-11-10 |
| JP4656838B2 (ja) | 2011-03-23 |
| RU2004126671A (ru) | 2005-04-10 |
| JP2005526028A (ja) | 2005-09-02 |
| AU2003215087A1 (en) | 2003-09-02 |
| US20040034037A1 (en) | 2004-02-19 |
| AU2003215087B2 (en) | 2009-07-16 |
| WO2003066629A3 (en) | 2003-10-30 |
| JP2010132697A (ja) | 2010-06-17 |
| EP2322521B1 (en) | 2013-09-04 |
| EP2322521A1 (en) | 2011-05-18 |
| CA2475633A1 (en) | 2003-08-14 |
| WO2003066629A2 (en) | 2003-08-14 |
| US20070270420A1 (en) | 2007-11-22 |
| SG159380A1 (en) | 2010-03-30 |
| EP1472245A2 (en) | 2004-11-03 |
| KR20040084896A (ko) | 2004-10-06 |
| NO20043726L (no) | 2004-11-08 |
| ES2437391T3 (es) | 2014-01-10 |
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| MKLA | Lapsed |
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