AR043420A1 - Biariltetrahidroisoquinolina piperidinas como antagonistas receptores selectivos de la mch, composiciones farmaceuticas que los contienen y su metodo de preparacion. - Google Patents
Biariltetrahidroisoquinolina piperidinas como antagonistas receptores selectivos de la mch, composiciones farmaceuticas que los contienen y su metodo de preparacion.Info
- Publication number
- AR043420A1 AR043420A1 ARP040100622A ARP040100622A AR043420A1 AR 043420 A1 AR043420 A1 AR 043420A1 AR P040100622 A ARP040100622 A AR P040100622A AR P040100622 A ARP040100622 A AR P040100622A AR 043420 A1 AR043420 A1 AR 043420A1
- Authority
- AR
- Argentina
- Prior art keywords
- nr8r9
- alkyl
- aryl
- heteroaryl
- cr8r8
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title 2
- 238000002360 preparation method Methods 0.000 title 1
- 125000003118 aryl group Chemical group 0.000 abstract 8
- 125000001072 heteroaryl group Chemical group 0.000 abstract 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract 5
- 239000001257 hydrogen Substances 0.000 abstract 5
- 125000000217 alkyl group Chemical group 0.000 abstract 4
- 101800002739 Melanin-concentrating hormone Proteins 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 abstract 3
- 102000047659 melanin-concentrating hormone Human genes 0.000 abstract 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 125000004475 heteroaralkyl group Chemical group 0.000 abstract 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 241000790917 Dioxys <bee> Species 0.000 abstract 1
- 208000030814 Eating disease Diseases 0.000 abstract 1
- 208000019454 Feeding and Eating disease Diseases 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 206010020710 Hyperphagia Diseases 0.000 abstract 1
- 208000008589 Obesity Diseases 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 235000014632 disordered eating Nutrition 0.000 abstract 1
- -1 ethylene dioxy Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 208000030159 metabolic disease Diseases 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 235000020824 obesity Nutrition 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Compuestos que son nuevos antagonistas para la hormona concentradora de melanina (MCH). Composiciones farmacéuticas que comprende dichos antagonistas de la MCH así como también los métodos para usarlos para tratar la obesidad, los trastornos metabólicos, los trastornos de la alimentación, tales como hiperfagia, y diabetes. Reivindicación 1: Un compuesto representado por la fórmula estructural (1), o una sal o solvato de dicho compuesto farmacéuticamente aceptable, una mezcla isomérica o racémica, en la cual: X es -CH2-, -S(O2)-, carbonilo, -CHCH3 o -C(CH2)2-; Y es -(CR2R3)p-, -(CR2R3)pC(O)NH-, -(CR2R3)pNH-, -C(O)NH-, -C(O)(CR2R3)pNH-, -C(O)C(O)NH- o -C(O)(CR2R3)p-; Z es arilo, heteroarilo, arilo R6 -sustituido o heteroarilo R6-sustituido; n es 0, 2 ó 3, y cuando n es 0, no existe ningún enlace conector entre los dos carbonos adyacentes al nitrógeno; p es 1, 2 ó 3, q es 1, 2, 3, 4, 5 ó 6; r es 0 ó 1 y cuando r es 0, X está ligado directamente al anillo aromático; R1 es hidrógeno, -acilo, -alquilo, -cicloalquilo, -alquilo sustituido con cicloalquilo, aralquilo, heteroaralquilo, -C(O)R5, -C(O)OR5, -C(O)OR8, -C(O)NR8R9, -S(O2)R5, -S(O2)NR8R9, cicloalquilalquilo, cicloalquilalquilo sustituido con R10 en el anillo -cicloalquio, heterociclilo, arilo, heteroarilo o -CF3; R2 y R3 pueden ser iguales o diferentes, siendo cada uno independientemente, hidrógeno, alcoxi o alquilo; o R2 y R3 pueden estar unidos conjuntamente con el carbono al cual están unidos para formar un anillo de 3 a 7 miembros; R4 es arilo, heteroarilo, arilo R7 -sustituido o heteroarilo R7- sustituido o Y -R4 tomados conjuntamente es una fórmula (2); R5 es alquilo, arilo, aralquilo, heteroarilo, cicloalquilo o heteroaralquilo; R6 es de 1 a 5 sustituyentes, cada R6 puede ser igual o diferentes y cada uno está independientemente seleccionado entre -OH, -alcoxi, -OCF3, -CN, -alquilo, halógeno, -NR8R9, -CONR8R9, -NR8S(O2)R6, -S(O2)NR8R9, -S(O2)R5, -COR5, -C(O)OR8, -CF3, -CHO, -C=NOR8, una fórmula (3), -(CR8R8)qNC(O)R11, -(CR8R8)qNS(O2)R12 y -(CR8R8)qNR8R9 donde los grupo R8 están independientemente seleccionados; R7 representa de 1 a 5 sustituyentes, cada R7 puede ser igual o diferente y cada uno está independientemente seleccionado entre hidrógeno, -OH, -alcoxi, -OCF3, -CN, -alquilo, halógeno, -NR8R9, -CONR8R9, -NR8S(O2)R6, -S(O2)NR8R9, -S(O2)R5, -COR5, -C(O)OR8, -CF3, -alquilenoNR8R9, -CHO, -C=NOR8, -NR8C(O)R5, o dos grupos R7 adyacentes pueden esta unidos conjuntamente con dos átomos de O para formar un grupo metileno dioxi o etileno dioxi, -(CR8R8)qNR8R9, -(CR8R8)qNC(O)R11 y -(CR8R8)qNS(O2)R12, donde los grupos R8 están independientemente seleccionados; R8 es hidrógeno o -alquilo; R9 es hidrógeno, -alquilo, -arilo o -heteroarilo; R10 es -OH, -alcoxi, -C(O)NR8R9, -NR8R9, -NR8S(O2)R5, -NR8C(O)NR8R9, -NR8C(O)R5, -NR8C(O)OR5, -C(O)OH o -C(O)OR5; R11 es alquilo, arilo o alcoxi-NR8R9; y R12 es alquilo, arilo o -NR8R9.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45079903P | 2003-02-28 | 2003-02-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR043420A1 true AR043420A1 (es) | 2005-07-27 |
Family
ID=32962533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP040100622A AR043420A1 (es) | 2003-02-28 | 2004-02-27 | Biariltetrahidroisoquinolina piperidinas como antagonistas receptores selectivos de la mch, composiciones farmaceuticas que los contienen y su metodo de preparacion. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7498441B2 (es) |
| EP (1) | EP1601664B1 (es) |
| JP (1) | JP4570165B2 (es) |
| CN (1) | CN1777596A (es) |
| AR (1) | AR043420A1 (es) |
| AT (1) | ATE393766T1 (es) |
| CA (1) | CA2517088A1 (es) |
| DE (1) | DE602004013427T2 (es) |
| ES (1) | ES2305735T3 (es) |
| MX (1) | MXPA05009193A (es) |
| TW (1) | TW200427679A (es) |
| WO (1) | WO2004078745A1 (es) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008094992A2 (en) * | 2007-01-31 | 2008-08-07 | Vertex Pharmaceuticals Incorporated | 2-aminopyridine derivatives useful as kinase inhibitors |
| ES2402087T3 (es) | 2008-07-23 | 2013-04-26 | Vertex Pharmaceuticals Incorporated | Inhibidores de la pirazolopiridina quinasa |
| US8569337B2 (en) | 2008-07-23 | 2013-10-29 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
| CN102131809A (zh) | 2008-07-23 | 2011-07-20 | 沃泰克斯药物股份有限公司 | 三环吡唑并吡啶激酶抑制剂 |
| JP2011530527A (ja) * | 2008-08-06 | 2011-12-22 | 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 | アミノピリジンキナーゼ阻害剤 |
| JP5627675B2 (ja) | 2009-05-06 | 2014-11-19 | 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 | ピラゾロピリジン |
| JP5769733B2 (ja) | 2010-01-27 | 2015-08-26 | 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 | ピラゾロピリジンキナーゼ阻害剤 |
| CA2787079A1 (en) | 2010-01-27 | 2011-08-04 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrazine kinase inhibitors |
| WO2011094290A1 (en) | 2010-01-27 | 2011-08-04 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrimidine kinase inhibitors |
| EP3395809A4 (en) * | 2015-12-22 | 2019-06-19 | Jiangsu Hengrui Medicine Co. Ltd. | BENZOPIPERIDIN DERIVATIVE, PRODUCTION METHOD AND MEDICAL USE THEREOF |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5908830A (en) * | 1996-10-31 | 1999-06-01 | Merck & Co., Inc. | Combination therapy for the treatment of diabetes and obesity |
| CZ298824B6 (cs) * | 1997-05-30 | 2008-02-20 | Neurosearch A/S | Deriváty 8-azabicyklo[3.2.1]okt-2-enu, zpusob jejich prípravy a jejich použití |
| EP1113007A1 (en) * | 1999-12-24 | 2001-07-04 | Pfizer Inc. | Tetrahydroisoquinoline compounds as estrogen agonists/antagonists |
| CA2384041A1 (en) * | 2000-07-05 | 2002-01-24 | Synaptic Pharmaceuticals Corporation | Selective melanin concentrating hormone-1 (mch1) receptor antagonists and uses thereof |
| PE20021081A1 (es) * | 2001-04-12 | 2002-12-18 | Pharmacopeia Drug Discovery | Aril y biaril piperidinas con actividad moduladora mch |
| EP1532147B1 (en) * | 2002-06-27 | 2006-08-02 | Schering Corporation | Spirosubstituted piperidines as selective melanin concentrating hormone receptor antagonists for the treatment of obesity |
-
2004
- 2004-02-26 DE DE602004013427T patent/DE602004013427T2/de not_active Expired - Lifetime
- 2004-02-26 CN CNA2004800109047A patent/CN1777596A/zh active Pending
- 2004-02-26 JP JP2006508855A patent/JP4570165B2/ja not_active Expired - Fee Related
- 2004-02-26 CA CA002517088A patent/CA2517088A1/en not_active Abandoned
- 2004-02-26 AT AT04715072T patent/ATE393766T1/de not_active IP Right Cessation
- 2004-02-26 MX MXPA05009193A patent/MXPA05009193A/es active IP Right Grant
- 2004-02-26 EP EP04715072A patent/EP1601664B1/en not_active Expired - Lifetime
- 2004-02-26 US US10/788,109 patent/US7498441B2/en not_active Expired - Fee Related
- 2004-02-26 WO PCT/US2004/005780 patent/WO2004078745A1/en active Application Filing
- 2004-02-26 TW TW093104942A patent/TW200427679A/zh unknown
- 2004-02-26 ES ES04715072T patent/ES2305735T3/es not_active Expired - Lifetime
- 2004-02-27 AR ARP040100622A patent/AR043420A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE602004013427T2 (de) | 2009-06-04 |
| MXPA05009193A (es) | 2005-10-18 |
| US20040176355A1 (en) | 2004-09-09 |
| CA2517088A1 (en) | 2004-09-16 |
| US7498441B2 (en) | 2009-03-03 |
| EP1601664A1 (en) | 2005-12-07 |
| DE602004013427D1 (de) | 2008-06-12 |
| ES2305735T3 (es) | 2008-11-01 |
| JP4570165B2 (ja) | 2010-10-27 |
| CN1777596A (zh) | 2006-05-24 |
| TW200427679A (en) | 2004-12-16 |
| JP2006520399A (ja) | 2006-09-07 |
| ATE393766T1 (de) | 2008-05-15 |
| EP1601664B1 (en) | 2008-04-30 |
| WO2004078745A1 (en) | 2004-09-16 |
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