JP4602667B2 - アゾール誘導体および該アゾール誘導体を含有する医薬組成物 - Google Patents
アゾール誘導体および該アゾール誘導体を含有する医薬組成物 Download PDFInfo
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- JP4602667B2 JP4602667B2 JP2003538142A JP2003538142A JP4602667B2 JP 4602667 B2 JP4602667 B2 JP 4602667B2 JP 2003538142 A JP2003538142 A JP 2003538142A JP 2003538142 A JP2003538142 A JP 2003538142A JP 4602667 B2 JP4602667 B2 JP 4602667B2
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- Prior art keywords
- alkyl
- imidazol
- ylmethyl
- iodo
- halogen
- 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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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 150000007980 azole derivatives Chemical class 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims description 156
- -1 alkoxy halogen Chemical class 0.000 claims description 68
- 125000001072 heteroaryl group Chemical group 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 150000002367 halogens Chemical class 0.000 claims description 58
- 238000011282 treatment Methods 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 206010028980 Neoplasm Diseases 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 125000002723 alicyclic group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 125000006413 ring segment Chemical group 0.000 claims description 7
- 239000005711 Benzoic acid Substances 0.000 claims description 6
- 235000010233 benzoic acid Nutrition 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- QQRKJVIRHXDXHB-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 QQRKJVIRHXDXHB-UHFFFAOYSA-N 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- CTQRYNQVNOXJOQ-UHFFFAOYSA-N (1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl) 4-iodobenzoate Chemical compound C1=CC(I)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CN=C1 CTQRYNQVNOXJOQ-UHFFFAOYSA-N 0.000 claims description 3
- AQABPIBXKWPEIJ-UHFFFAOYSA-N [1-(2-methylimidazol-1-yl)-3-(oxan-2-yloxy)propan-2-yl] 4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C=CC(I)=CC=1)COC1OCCCC1 AQABPIBXKWPEIJ-UHFFFAOYSA-N 0.000 claims description 3
- ZQSZSWQNEFVKGG-UHFFFAOYSA-N [1-(cyclopropylmethoxy)-3-(2-methylimidazol-1-yl)propan-2-yl] 2-chloro-4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C(=CC(I)=CC=1)Cl)COCC1CC1 ZQSZSWQNEFVKGG-UHFFFAOYSA-N 0.000 claims description 3
- NCRBSVCFQVEWOV-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-(1,2,4-triazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1N=CN=C1 NCRBSVCFQVEWOV-UHFFFAOYSA-N 0.000 claims description 3
- UHZIEFLWILBLGZ-UHFFFAOYSA-N (1-imidazol-1-yl-3-methoxypropan-2-yl) 4-iodobenzoate Chemical compound C=1C=C(I)C=CC=1C(=O)OC(COC)CN1C=CN=C1 UHZIEFLWILBLGZ-UHFFFAOYSA-N 0.000 claims description 2
- CVSDGUSPTSMQBJ-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 3-methoxybenzoate Chemical compound COC1=CC=CC(C(=O)OC(COC=2C=CC=CC=2)CN2C=NC=C2)=C1 CVSDGUSPTSMQBJ-UHFFFAOYSA-N 0.000 claims description 2
- WXGSSMRODDWZFH-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-(trifluoromethyl)benzoate Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 WXGSSMRODDWZFH-UHFFFAOYSA-N 0.000 claims description 2
- FULGRUKJYJWJDF-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-bromo-2-chlorobenzoate Chemical compound ClC1=CC(Br)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 FULGRUKJYJWJDF-UHFFFAOYSA-N 0.000 claims description 2
- FCNIAPWYVGTYIT-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-bromobenzoate Chemical compound C1=CC(Br)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 FCNIAPWYVGTYIT-UHFFFAOYSA-N 0.000 claims description 2
- ZRFIFBBEQSGQFS-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-fluorobenzoate Chemical compound C1=CC(F)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 ZRFIFBBEQSGQFS-UHFFFAOYSA-N 0.000 claims description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 2
- QKKVAIYZXGCQAN-UHFFFAOYSA-N 2-(difluoromethyl)-1h-imidazole Chemical compound FC(F)C1=NC=CN1 QKKVAIYZXGCQAN-UHFFFAOYSA-N 0.000 claims description 2
- HJMOACBJSLAGME-UHFFFAOYSA-N 2-chloro-n-(1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl)-4-iodobenzamide Chemical compound ClC1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CN=C1 HJMOACBJSLAGME-UHFFFAOYSA-N 0.000 claims description 2
- DKDCTJRPQBGCFM-UHFFFAOYSA-N 2-chloro-n-[1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C(=CC(I)=CC=1)Cl)CN1C=NC=C1 DKDCTJRPQBGCFM-UHFFFAOYSA-N 0.000 claims description 2
- VTSBOMMVBCCYNZ-UHFFFAOYSA-N [1-(4-acetamidophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-iodobenzoate Chemical compound C1=CC(NC(=O)C)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 VTSBOMMVBCCYNZ-UHFFFAOYSA-N 0.000 claims description 2
- DKQCXNIDGIPIBX-UHFFFAOYSA-N [1-(4-cyanophenoxy)-3-(2-methylimidazol-1-yl)propan-2-yl] 4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(C#N)C=C1 DKQCXNIDGIPIBX-UHFFFAOYSA-N 0.000 claims description 2
- JTNXYKMQMWRALS-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-(1,2,4-triazol-1-yl)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1N=CN=C1 JTNXYKMQMWRALS-UHFFFAOYSA-N 0.000 claims description 2
- MYYLIMLHXIIIMZ-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 2,4-dichlorobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 MYYLIMLHXIIIMZ-UHFFFAOYSA-N 0.000 claims description 2
- SGWCLRZNWVPFJX-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-iodobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 SGWCLRZNWVPFJX-UHFFFAOYSA-N 0.000 claims description 2
- VUIUMNPJDNTIKP-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=C(F)C=C1 VUIUMNPJDNTIKP-UHFFFAOYSA-N 0.000 claims description 2
- GUUSBVNDBCVAIS-UHFFFAOYSA-N [1-imidazol-1-yl-3-(2-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 GUUSBVNDBCVAIS-UHFFFAOYSA-N 0.000 claims description 2
- YOPNHJJETCAFCE-UHFFFAOYSA-N [1-imidazol-1-yl-3-(3-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound [O-][N+](=O)C1=CC=CC(OCC(CN2C=NC=C2)OC(=O)C=2C=CC(I)=CC=2)=C1 YOPNHJJETCAFCE-UHFFFAOYSA-N 0.000 claims description 2
- XCWWZSYUAYVVMT-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-iodophenoxy)propan-2-yl] 4-bromo-2-chlorobenzoate Chemical compound C1=CC(=CC=C1OCC(CN2C=CN=C2)OC(=O)C3=C(C=C(C=C3)Br)Cl)I XCWWZSYUAYVVMT-UHFFFAOYSA-N 0.000 claims description 2
- CCKLUXJAXAWORF-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-iodophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC(I)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 CCKLUXJAXAWORF-UHFFFAOYSA-N 0.000 claims description 2
- LZBOKYSSRYQASV-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-iodophenoxy)propan-2-yl] 4-methoxybenzoate Chemical compound COC1=CC=C(C=C1)C(=O)OC(CN2C=CN=C2)COC3=CC=C(C=C3)I LZBOKYSSRYQASV-UHFFFAOYSA-N 0.000 claims description 2
- DPTLLKCIWYDYRY-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-methoxyphenoxy)propan-2-yl] 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1OCC(OC(=O)C=1C=CC(OC)=CC=1)CN1C=NC=C1 DPTLLKCIWYDYRY-UHFFFAOYSA-N 0.000 claims description 2
- JTWITXSRBQCTHA-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 JTWITXSRBQCTHA-UHFFFAOYSA-N 0.000 claims description 2
- DRHNPUWRASFLHB-UHFFFAOYSA-N [3-imidazol-1-yl-2-(4-iodobenzoyl)oxy-2-methylpropyl] 4-nitrobenzoate Chemical compound C1=CN=CN1CC(OC(=O)C=1C=CC(I)=CC=1)(C)COC(=O)C1=CC=C([N+]([O-])=O)C=C1 DRHNPUWRASFLHB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- DLSUFMMWXXPUHP-UHFFFAOYSA-N n-(1-imidazol-1-yl-3-phenoxypropan-2-yl)-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CC=C1 DLSUFMMWXXPUHP-UHFFFAOYSA-N 0.000 claims description 2
- QAWIWTFXLCFEOO-UHFFFAOYSA-N n-(1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl)-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CN=C1 QAWIWTFXLCFEOO-UHFFFAOYSA-N 0.000 claims description 2
- SVOVZDKVCARNGV-UHFFFAOYSA-N n-(3-imidazol-1-yl-2-phenoxypropyl)-4-iodo-n-methylbenzamide Chemical compound C=1C=C(I)C=CC=1C(=O)N(C)CC(OC=1C=CC=CC=1)CN1C=CN=C1 SVOVZDKVCARNGV-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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| US33604001P | 2001-10-23 | 2001-10-23 | |
| PCT/US2002/033963 WO2003035626A2 (en) | 2001-10-23 | 2002-10-23 | Azole derivatives and pharmaceutical compositions containing them |
Publications (3)
| Publication Number | Publication Date |
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| JP2005508972A JP2005508972A (ja) | 2005-04-07 |
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| IL (1) | IL161580A0 (enExample) |
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| US7253199B2 (en) * | 2001-10-23 | 2007-08-07 | Applied Research Systems Ars Holding N.V. | Azole derivatives and pharmaceutical compositions containing them |
| AR051248A1 (es) | 2004-10-20 | 2007-01-03 | Applied Research Systems | Derivados de 3-arilamino piridina |
| US8546404B2 (en) | 2005-12-13 | 2013-10-01 | Merck Sharp & Dohme | Compounds that are ERK inhibitors |
| ES2353437T3 (es) | 2006-02-16 | 2011-03-02 | Schering Corporation | Derivados de pirrolidina como inhibidores de erk. |
| SG188179A1 (en) | 2008-02-21 | 2013-03-28 | Merck Sharp & Dohme | Compounds that are erk inhibitors |
| US8951979B2 (en) * | 2008-06-13 | 2015-02-10 | Cornell University | Pain treatment using ERK2 inhibitors |
| WO2010051933A2 (en) | 2008-11-10 | 2010-05-14 | Bayer Schering Pharma Aktiengesellschaft | Substituted sulphonamido phenoxybenzamides |
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| US8962606B2 (en) | 2009-10-21 | 2015-02-24 | Bayer Intellectual Property Gmbh | Substituted benzosulphonamides |
| CA2777071A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted halophenoxybenzamide derivatives |
| CA2777430A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| AU2011224410B2 (en) | 2010-03-09 | 2015-05-28 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
| US9045429B2 (en) | 2010-10-29 | 2015-06-02 | Bayer Intellectual Property Gmbh | Substituted phenoxypyridines |
| WO2013109142A1 (en) | 2012-01-16 | 2013-07-25 | Stichting Het Nederlands Kanker Instituut | Combined pdk and mapk/erk pathway inhibition in neoplasia |
| US20150141470A1 (en) | 2012-05-08 | 2015-05-21 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
| EP3046557A1 (en) | 2013-09-20 | 2016-07-27 | Stichting Het Nederlands Kanker Instituut | Rock in combination with mapk-pathway |
| WO2015041534A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | P90rsk in combination with raf/erk/mek |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| WO2015178770A1 (en) | 2014-05-19 | 2015-11-26 | Stichting Het Nederlands Kanker Instituut | Compositions for cancer treatment |
| EP3355923B1 (en) | 2015-10-01 | 2022-02-23 | Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis | Histone deacetylase inhibitors for use in the treatment of drug resistant melanoma |
| WO2017099591A1 (en) | 2015-12-07 | 2017-06-15 | Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis | Treatment of inhibitor resistant braf-mutant cancers |
| WO2017204626A1 (en) | 2016-05-24 | 2017-11-30 | Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis | Combination therapy - combined map2k4/map3k1 and mek/erk inhibition |
| WO2021018866A1 (en) * | 2019-07-30 | 2021-02-04 | Edvince Ab | Mek inhibitor for treatment of stroke |
| CN110845703A (zh) * | 2019-10-28 | 2020-02-28 | 上海瀚岱化学有限公司 | 一种水性环氧树脂及其制备方法 |
| CN110903735A (zh) * | 2019-11-11 | 2020-03-24 | 上海瀚岱化学有限公司 | 一种水性环氧涂料及其制备方法与应用 |
| EP4142878B1 (en) | 2020-04-28 | 2024-06-26 | The Regents of The University of Michigan | Pyridine inhibitors of glucosylceramide synthase and therapeutic methods using the same |
| CN112759742A (zh) * | 2020-12-18 | 2021-05-07 | 江西瀚泰新材料科技有限公司 | 一种增韧型水性环氧树脂及其制备方法 |
| CN112794989A (zh) * | 2020-12-18 | 2021-05-14 | 江西瀚泰新材料科技有限公司 | 一种增韧阻燃水性环氧树脂及其制备方法 |
| CN112646123A (zh) * | 2020-12-18 | 2021-04-13 | 江西瀚泰新材料科技有限公司 | 一种低粘度水性环氧树脂及其制备方法 |
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| CA1271477A (en) * | 1983-11-18 | 1990-07-10 | John F. Gerster | 1h-imidazo[4,5-c]quinolin-4-amines |
| PL195600B1 (pl) * | 1998-05-15 | 2007-10-31 | Astrazeneca Ab | Pochodne benzamidowe, sposób ich wytwarzania, zawierające je kompozycje farmaceutyczne oraz ich zastosowanie do wytwarzania leku do leczenia stanów medycznych powstających za pośrednictwem cytokin |
| US6599910B1 (en) * | 1998-08-20 | 2003-07-29 | Smithkline Beecham Corporation | Substituted triazole compounds |
| AP2001002225A0 (en) * | 1999-01-13 | 2001-09-30 | Warner Lambert Co | 1-heterocycle substituted diarylamines. |
| US7253199B2 (en) * | 2001-10-23 | 2007-08-07 | Applied Research Systems Ars Holding N.V. | Azole derivatives and pharmaceutical compositions containing them |
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- 2002-10-23 CA CA002463101A patent/CA2463101A1/en not_active Abandoned
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- 2008-06-20 AU AU2008202731A patent/AU2008202731A1/en not_active Abandoned
Also Published As
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| JP2005508972A (ja) | 2005-04-07 |
| EP2332922A1 (en) | 2011-06-15 |
| EP1438295A2 (en) | 2004-07-21 |
| AU2002359291C1 (en) | 2008-11-20 |
| US20070293555A1 (en) | 2007-12-20 |
| US7541375B2 (en) | 2009-06-02 |
| EP1438295B1 (en) | 2012-08-15 |
| AU2002359291B2 (en) | 2008-04-03 |
| US20050054706A1 (en) | 2005-03-10 |
| AU2008202731A1 (en) | 2008-07-17 |
| WO2003035626A3 (en) | 2003-11-06 |
| IL161580A0 (en) | 2004-09-27 |
| US7253199B2 (en) | 2007-08-07 |
| AU2002359291B8 (en) | 2008-04-17 |
| CA2463101A1 (en) | 2003-05-01 |
| ES2393186T3 (es) | 2012-12-19 |
| WO2003035626A2 (en) | 2003-05-01 |
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