CA2604463C - 3-amino-pyrazolo[3,4b]pyridines as inhibitors of protein tyrosine kinases, their production and use as pharmaceutical agents - Google Patents
3-amino-pyrazolo[3,4b]pyridines as inhibitors of protein tyrosine kinases, their production and use as pharmaceutical agents Download PDFInfo
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- CA2604463C CA2604463C CA2604463A CA2604463A CA2604463C CA 2604463 C CA2604463 C CA 2604463C CA 2604463 A CA2604463 A CA 2604463A CA 2604463 A CA2604463 A CA 2604463A CA 2604463 C CA2604463 C CA 2604463C
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- stands
- alkyl
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- substituted
- ring
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 221
- 239000008177 pharmaceutical agent Substances 0.000 title claims description 19
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 12
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 12
- 239000003112 inhibitor Substances 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 222
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 25
- -1 C3-C10-cycloalkyl Chemical group 0.000 claims description 148
- 125000001072 heteroaryl group Chemical group 0.000 claims description 127
- 125000003118 aryl group Chemical group 0.000 claims description 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- 229910052736 halogen Inorganic materials 0.000 claims description 99
- 150000002367 halogens Chemical class 0.000 claims description 99
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 96
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 91
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 84
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 84
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 44
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
- 239000012453 solvate Substances 0.000 claims description 38
- 229910052717 sulfur Inorganic materials 0.000 claims description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 37
- 239000011593 sulfur Substances 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 35
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 239000001301 oxygen Substances 0.000 claims description 35
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 125000004429 atom Chemical group 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 25
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001041 indolyl group Chemical group 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 125000003944 tolyl group Chemical group 0.000 claims description 15
- 125000002883 imidazolyl group Chemical group 0.000 claims description 14
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 125000002757 morpholinyl group Chemical group 0.000 claims description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 230000001154 acute effect Effects 0.000 claims description 9
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- 230000004770 neurodegeneration Effects 0.000 claims description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
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- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 230000035168 lymphangiogenesis Effects 0.000 claims description 8
- 230000004862 vasculogenesis Effects 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 208000019553 vascular disease Diseases 0.000 claims description 7
- 125000004799 bromophenyl group Chemical group 0.000 claims description 6
- 125000004188 dichlorophenyl group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
- 239000013067 intermediate product Substances 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 4
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 238000000376 autoradiography Methods 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 4
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims 3
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 3
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 108
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- 101150041968 CDC13 gene Proteins 0.000 description 83
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 83
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 80
- 239000000126 substance Substances 0.000 description 71
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 45
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 38
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
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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 24
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| DE102004061288.9 | 2004-12-14 | ||
| DE102004061288A DE102004061288A1 (de) | 2004-12-14 | 2004-12-14 | 3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel |
| US63669004P | 2004-12-17 | 2004-12-17 | |
| US60/636,690 | 2004-12-17 | ||
| PCT/EP2005/013417 WO2006063805A1 (de) | 2004-12-14 | 2005-12-12 | 3-amino-pyrazolo[3,4b]pyridine als inhibitoren von proteintyrosinkinasen zur behandlung von angiogen, hyperproliferativen oder neurodegenerativen erkrankungen |
Publications (2)
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| CA2604463A1 CA2604463A1 (en) | 2006-06-22 |
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| PE (1) | PE20060737A1 (enExample) |
| TW (1) | TW200634012A (enExample) |
| UY (1) | UY29253A1 (enExample) |
| WO (1) | WO2006063805A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| EP1980561B1 (en) * | 2007-03-30 | 2013-10-09 | Nerviano Medical Sciences S.R.L. | Substituted 1h-pyrazolo[3,4-b] pyridine derivatives active as kinase inhibitors |
| TW200922566A (en) | 2007-09-14 | 2009-06-01 | Ortho Mcneil Janssen Pharm | 1,3 disubstituted 4-(aryl-X-phenyl)-1H-pyridin-2-ones |
| EA017648B1 (ru) | 2007-09-14 | 2013-02-28 | Орто-Макнейл-Янссен Фармасьютикалз, Инк. | 1',3'-двузамещенные-4-фенил-3,4,5,6-тетрагидро-2н,1'н-[1,4']бипириди-нил-2'-оны |
| BRPI0816970A2 (pt) | 2007-09-14 | 2015-03-24 | Ortho Mcneil Janssen Pharm | 1,3-dissubstituídas-4-fenil-1h-piridin-2-onas |
| US8173635B2 (en) * | 2007-11-02 | 2012-05-08 | Vertex Pharmaceuticals Incorporated | Kinase inhibitors |
| CA2704436C (en) | 2007-11-14 | 2016-01-05 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| 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 |
| WO2010043396A1 (en) | 2008-10-16 | 2010-04-22 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
| JP5690277B2 (ja) | 2008-11-28 | 2015-03-25 | 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インドールおよびベンゾオキサジン誘導体 |
| 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 |
| HRP20131122T1 (hr) | 2009-05-12 | 2013-12-20 | Janssen Pharmaceuticals, Inc. | Derivati 1,2,4-triazolo[4,3-a] piridina i njihova uporaba u lijeäśenju ili prevenciji neuroloških i psihijatrijskih poremeä†aja |
| CN102439015B (zh) | 2009-05-12 | 2015-05-13 | 杨森制药有限公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物和其作为mGluR2受体的正向变构调节剂的用途 |
| WO2011019780A1 (en) | 2009-08-11 | 2011-02-17 | Bristol-Myers Squibb Company | Azaindazoles as btk kinase modulators and use thereof |
| ES2460915T3 (es) | 2009-12-21 | 2014-05-16 | Novartis Ag | Piridinas fusionadas con heteroarilo disustituido |
| JP2013534539A (ja) | 2010-07-15 | 2013-09-05 | ブリストル−マイヤーズ スクイブ カンパニー | アザインダゾール化合物 |
| JP5852664B2 (ja) | 2010-11-08 | 2016-02-03 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | １，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用 |
| ES2536433T3 (es) | 2010-11-08 | 2015-05-25 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| FR2970967B1 (fr) * | 2011-01-27 | 2013-02-15 | Pf Medicament | Derives de type azaindazole ou diazaindazole comme medicament |
| FR2984325A1 (fr) * | 2011-12-14 | 2013-06-21 | Sanofi Sa | Derives de pyrazolopyridine, leur procede de preparation et leur application en therapeutique |
| US10138235B2 (en) | 2011-12-14 | 2018-11-27 | Sanofi | Pyrazolopyridine derivatives, preparation process therefor and therapeutic use thereof |
| EP2689778A1 (en) * | 2012-07-27 | 2014-01-29 | Pierre Fabre Medicament | Derivatives of azaindoles or diazaindoles for treating pain |
| 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 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| ME03518B (me) | 2014-01-21 | 2020-04-20 | Janssen Pharmaceutica Nv | Kombinacije koje obuhvataju pozitivne alosterične modulatore ili ortosterične agoniste metabotropnog glutamatergičnog receptora podtipa 2 i njihova primjena |
| PL3096790T3 (pl) | 2014-01-21 | 2020-01-31 | Janssen Pharmaceutica, N.V. | Kombinacje zawierające pozytywne modulatory allosteryczne lub agonistów ortosterycznych metabotropowego receptora glutaminergicznego podtypu 2 i ich zastosowanie |
| WO2024211708A1 (en) * | 2023-04-06 | 2024-10-10 | Myrobalan Therapeutics, Inc. | Tyk2 inhibitors for treatment of glaucoma |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2160780A1 (de) | 1971-12-08 | 1973-06-14 | Basf Ag | Pyridino-pyrazole |
| DE2238400A1 (de) * | 1972-08-04 | 1974-02-14 | Hoechst Ag | Basische azofarbstoffe, verfahren zu ihrer herstellung und ihre verwendung |
| DE2355967A1 (de) | 1973-11-09 | 1975-07-24 | Hoechst Ag | Polycyclische farbstoffe, verfahren zu ihrer herstellung und ihre verwendung |
| DE2643753A1 (de) * | 1976-09-29 | 1978-04-06 | Thomae Gmbh Dr K | Neue 1h-pyrazolo eckige klammer auf 3,4-b eckige klammer zu pyridine |
| DE3001498A1 (de) * | 1980-01-17 | 1981-07-23 | Agfa-Gevaert Ag, 5090 Leverkusen | Fotografisches material mit einem stabilisierungsmittel, verfahren zu dessen herstellung, ein entwicklungsverfahren, neue pyrazole, ein verfahren zu deren herstellung sowie zwischenprodukte |
| US5478830A (en) * | 1992-05-29 | 1995-12-26 | The Du Pont Merck Pharmaceutical Company | Fused-ring heterocycles for the treatment of atherosclerosis |
| US6046216A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyridinone derivatives |
| HK1053831A1 (zh) * | 1999-09-17 | 2003-11-07 | Basf Aktiengesellschaft | 作为治疗药物的激酶抑制剂 |
| HUP0700086A2 (en) * | 2000-08-11 | 2007-05-29 | Eisai Co Ltd | 2-aminopyridine compounds, use thereof as drugs and pharmaceutical compositions containing them |
| JP4272338B2 (ja) * | 2000-09-22 | 2009-06-03 | バイエル アクチェンゲゼルシャフト | ピリジン誘導体 |
| FR2827603B1 (fr) | 2001-07-18 | 2003-10-17 | Oreal | Composes derives de diaminopyrazole substitues par un radical heteroaromatique et leur utilisation en teinture d'oxydation des fibres keratiniques |
| ES2266618T3 (es) * | 2001-08-23 | 2007-03-01 | Bayer Cropscience S.A. | Propargilaminas substituidas. |
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Also Published As
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| US7977325B2 (en) | 2011-07-12 |
| PE20060737A1 (es) | 2006-08-17 |
| PA8656401A1 (es) | 2006-07-03 |
| GT200500363A (es) | 2006-11-27 |
| UY29253A1 (es) | 2006-06-30 |
| CA2604463A1 (en) | 2006-06-22 |
| EP1846402B1 (de) | 2014-02-26 |
| AR051794A1 (es) | 2007-02-07 |
| TW200634012A (en) | 2006-10-01 |
| EP1846402A1 (de) | 2007-10-24 |
| JP2008523018A (ja) | 2008-07-03 |
| DE102004061288A1 (de) | 2006-06-29 |
| US20090030010A1 (en) | 2009-01-29 |
| WO2006063805A1 (de) | 2006-06-22 |
| DOP2005000251A (es) | 2006-06-30 |
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