KR20080060286A - 진정 및 운동실조 효과가 감소된 항불안제 - Google Patents
진정 및 운동실조 효과가 감소된 항불안제 Download PDFInfo
- Publication number
- KR20080060286A KR20080060286A KR1020087012062A KR20087012062A KR20080060286A KR 20080060286 A KR20080060286 A KR 20080060286A KR 1020087012062 A KR1020087012062 A KR 1020087012062A KR 20087012062 A KR20087012062 A KR 20087012062A KR 20080060286 A KR20080060286 A KR 20080060286A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- compound
- phenyl
- thienyl
- cyclopropyl
- 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.)
- Ceased
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- 230000002829 reductive effect Effects 0.000 title abstract description 73
- 230000000694 effects Effects 0.000 title abstract description 39
- 239000002249 anxiolytic agent Substances 0.000 title abstract description 20
- 206010003591 Ataxia Diseases 0.000 title abstract description 10
- 229940125713 antianxiety drug Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 125000001424 substituent group Chemical group 0.000 claims abstract description 58
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 51
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 34
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 32
- 229910004013 NO 2 Inorganic materials 0.000 claims abstract description 25
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 25
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 25
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 25
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 25
- 125000006430 alkyl cyclopropyl group Chemical group 0.000 claims abstract description 7
- -1 CH 3 Chemical group 0.000 claims description 50
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 claims description 2
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 claims description 2
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- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 abstract description 2
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 11
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 10
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
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- 230000006399 behavior Effects 0.000 description 8
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- HZYHQJXUEKIREU-UHFFFAOYSA-N ethyl 8-ethynyl-6-phenyl-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound CCOC(=O)C=1N=CN(C2=CC=C(C=C22)C#C)C=1CN=C2C1=CC=CC=C1 HZYHQJXUEKIREU-UHFFFAOYSA-N 0.000 description 8
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- JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 7
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
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- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
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- 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
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- 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
- C07D487/06—Peri-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| USRE47475E1 (en) * | 2002-03-28 | 2019-07-02 | Wisys Technology Foundation, Inc. | Selective agents for pain suppression |
| US7618958B2 (en) | 2004-06-30 | 2009-11-17 | Wisys Technology Foundation, Inc. | Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects |
| US8119629B2 (en) | 2007-10-03 | 2012-02-21 | Bristol-Meyers Squibb Company | Carboxamide GABAA α2 modulators |
| WO2009094260A1 (en) * | 2008-01-22 | 2009-07-30 | Eli Lilly And Company | Kappa selective opioid receptor antagonist |
| US20100261711A1 (en) * | 2009-03-20 | 2010-10-14 | Wisys Technology Foundation | Selective anticonvulsant agents and their uses |
| JP2013209292A (ja) * | 2010-07-23 | 2013-10-10 | Nippon Chemiphar Co Ltd | Ｐ２ｘ４受容体拮抗剤 |
| US9006233B2 (en) | 2011-04-28 | 2015-04-14 | Uwm Research Foundation, Inc. | Gabaergic receptor subtype selective ligands and their uses |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| WO2014047413A1 (en) | 2012-09-21 | 2014-03-27 | Uwm Research Foundation, Inc. | Novel gabaa agonists and methods of using to control airway hyperresponsiveness and inflammation in asthma |
| FR3010785B1 (fr) * | 2013-09-18 | 2015-08-21 | Snecma | Procede de controle de la densite d'energie d'un faisceau laser par analyse d'image et dispositif correspondant |
| WO2017129801A1 (en) | 2016-01-27 | 2017-08-03 | Universität Zürich | Use of gabaa receptor modulators for treatment of itch |
| HRP20221098T1 (hr) | 2016-03-18 | 2022-11-25 | Uwm Research Foundation, Inc. | Tretman kognitivnih i simptoma poremećaja raspoloženja kod neurodegenerativnih i neuropsihijatrijskih poremećaja agonistima gabaa receptora koji sadrže alfa5 |
| CN109790170B (zh) | 2016-08-16 | 2022-08-02 | Uwm研究基金会有限公司 | Gaba(a)受体调节剂和控制哮喘中气道高反应性和炎症的方法 |
| WO2018083051A1 (en) * | 2016-11-01 | 2018-05-11 | F. Hoffmann-La Roche Ag | 1,3-dihydro-1,4-benzodiazepine-2-thiones for the treatment of cns related diseases |
| CN107056760A (zh) * | 2017-01-22 | 2017-08-18 | 苏州楚凯药业有限公司 | 5,7位取代的1H‑苯并[e][1,4]二氮杂‑2(3H)‑酮衍生物的制备方法 |
| CN107325101B (zh) * | 2017-06-29 | 2019-03-26 | 上海合全药物研发有限公司 | 6-羟甲基-6,7-二氢-5h,9h-咪唑并二氮杂卓-8-羧酸叔丁酯的合成方法 |
| CN107216332B (zh) * | 2017-06-29 | 2019-04-30 | 上海药明康德新药开发有限公司 | 叔丁基-7-羟甲基-7,8-二氢4h吡唑并二氮杂卓5(6h)甲酸基酯的合成方法 |
| WO2019070910A1 (en) | 2017-10-03 | 2019-04-11 | Uwm Research Foundation, Inc. | NEW POLYTHERAPY FOR ANXIETY, EPILEPSY AND PAIN DISORDERS |
| UA129503C2 (uk) | 2020-03-31 | 2025-05-14 | Ф. Хоффманн-Ля Рош Аг | ПОХІДНІ БЕНЗОДІАЗЕПІНУ ЯК ПОЗИТИВНІ АЛОСТЕРИЧНІ МОДУЛЯТОРИ ГАМК<sub>A</sub> ГАММА-1 |
| US12161622B2 (en) | 2021-05-04 | 2024-12-10 | Janssen Pharmaceuticals, Inc. | Compositions and methods for the treatment of depression |
| AR127127A1 (es) * | 2021-09-24 | 2023-12-20 | Hoffmann La Roche | NUEVOS DERIVADOS DE PIRIDODIAZEPINAS COMO PAM DE GABAA g1 |
| JP2024537773A (ja) | 2021-09-29 | 2024-10-16 | エフ． ホフマン－ラ ロシュ アーゲー | ＧＡＢＡ Ａγ１ ＰＡＭとしての新規ベンゾジアゼピン誘導体 |
| KR20240073892A (ko) | 2021-10-06 | 2024-05-27 | 에프. 호프만-라 로슈 아게 | Gaba a gamma1 수용체의 양성 알로스테릭 조절인자로서의 벤조디아제핀 유도체 |
| CN119156211A (zh) | 2022-03-07 | 2024-12-17 | 杨森制药公司 | 用于治疗重性抑郁障碍的多晶型形式的阿替卡普兰 |
| EP4489730B1 (en) | 2022-03-07 | 2026-01-21 | Janssen Pharmaceuticals, Inc. | Compositions comprising aticaprant |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2893992A (en) * | 1959-07-07 | I ii i i | ||
| US3886141A (en) * | 1971-10-07 | 1975-05-27 | Hoffmann La Roche | Preparation of 5-pyridyl benzodiazepine utilizing hexamethylenetetramine |
| US4280957A (en) | 1974-09-11 | 1981-07-28 | Hoffmann-La Roche Inc. | Imidazodiazepines and processes therefor |
| US4440685A (en) * | 1974-09-11 | 1984-04-03 | Hoffmann-La Roche Inc. | Imidazodiazepines and processes therefor |
| US4401597A (en) | 1978-05-15 | 1983-08-30 | Hoffmann-La Roche Inc. | Imidazodiazepines and processes therefor |
| DE3435973A1 (de) * | 1984-10-01 | 1986-04-10 | Boehringer Ingelheim KG, 6507 Ingelheim | Diazepine enthaltende pharmazeutische zusammensetzungen mit paf-antagonistischer wirkung |
| DE3778559D1 (de) * | 1986-01-21 | 1992-06-04 | Boehringer Ingelheim Kg | Thieno-1,4-diazepine. |
| US4959361A (en) | 1987-12-18 | 1990-09-25 | Hoffmann-La Roche Inc. | Triazolo(4,3-A)(1,4)benzodiazepines and thieno (3,2-F)(1,2,4)triazolo(4,3-A)(1,4)diazepine compounds which have useful activity as platelet activating factor (PAF) antagonists |
| MC1999A1 (fr) * | 1987-12-18 | 1990-01-26 | Hoffmann La Roche | Composes tricycliques |
| US5968176A (en) * | 1997-05-29 | 1999-10-19 | 3Com Corporation | Multilayer firewall system |
| CA2442557C (en) * | 2001-04-12 | 2008-12-23 | F. Hoffmann-La Roche Ag | Dihydro-benzo¬b|¬1,4|diazepin-2-one derivatives as mglur2 antagonists ii |
| US7161904B2 (en) * | 2002-06-04 | 2007-01-09 | Fortinet, Inc. | System and method for hierarchical metering in a virtual router based network switch |
| US7415723B2 (en) * | 2002-06-11 | 2008-08-19 | Pandya Ashish A | Distributed network security system and a hardware processor therefor |
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- 2003-03-28 KR KR1020087012062A patent/KR20080060286A/ko not_active Ceased
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- 2003-03-28 WO PCT/US2003/009587 patent/WO2003082832A2/en not_active Ceased
- 2003-03-28 IL IL16395803A patent/IL163958A0/xx unknown
- 2003-03-28 US US10/402,538 patent/US7119196B2/en not_active Expired - Lifetime
- 2003-03-28 EP EP03723846A patent/EP1490344B1/en not_active Expired - Lifetime
- 2003-03-28 AU AU2003230754A patent/AU2003230754B2/en not_active Ceased
- 2003-03-28 CA CA002480869A patent/CA2480869A1/en not_active Abandoned
- 2003-03-28 KR KR1020047015305A patent/KR100865410B1/ko not_active Expired - Fee Related
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| US7119196B2 (en) | 2006-10-10 |
| CA2480869A1 (en) | 2003-10-09 |
| BR0308918A (pt) | 2005-01-04 |
| WO2003082832A3 (en) | 2004-04-08 |
| EP1490344A2 (en) | 2004-12-29 |
| WO2003082832A2 (en) | 2003-10-09 |
| AU2003230754B2 (en) | 2007-10-25 |
| US20080108605A1 (en) | 2008-05-08 |
| US20070049580A1 (en) | 2007-03-01 |
| CN1642924A (zh) | 2005-07-20 |
| JP2005525392A (ja) | 2005-08-25 |
| KR100865410B1 (ko) | 2008-10-24 |
| DE60319812T2 (de) | 2009-04-23 |
| MXPA04009332A (es) | 2005-12-12 |
| US7235656B2 (en) | 2007-06-26 |
| US20100130481A1 (en) | 2010-05-27 |
| ES2300576T3 (es) | 2008-06-16 |
| ATE389640T1 (de) | 2008-04-15 |
| DE60319812D1 (de) | 2008-04-30 |
| EP1490344B1 (en) | 2008-03-19 |
| DK1490344T3 (da) | 2008-06-16 |
| US20070299058A1 (en) | 2007-12-27 |
| KR20040098029A (ko) | 2004-11-18 |
| IL163958A0 (en) | 2005-12-18 |
| AU2003230754A1 (en) | 2003-10-13 |
| NZ535517A (en) | 2007-02-23 |
| US20070054881A1 (en) | 2007-03-08 |
| US20040082573A1 (en) | 2004-04-29 |
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