CA2489681A1 - Aryl boronic acids for treating obesity - Google Patents
Aryl boronic acids for treating obesity Download PDFInfo
- Publication number
- CA2489681A1 CA2489681A1 CA002489681A CA2489681A CA2489681A1 CA 2489681 A1 CA2489681 A1 CA 2489681A1 CA 002489681 A CA002489681 A CA 002489681A CA 2489681 A CA2489681 A CA 2489681A CA 2489681 A1 CA2489681 A1 CA 2489681A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- substituted
- groups
- ammonium
- optionally
- 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.)
- Abandoned
Links
- 208000008589 Obesity Diseases 0.000 title claims abstract description 20
- 235000020824 obesity Nutrition 0.000 title claims abstract description 20
- 150000001543 aryl boronic acids Chemical class 0.000 title description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 34
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 150000001412 amines Chemical class 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 125000006575 electron-withdrawing group Chemical group 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 10
- 150000003568 thioethers Chemical class 0.000 claims abstract description 10
- 239000003085 diluting agent Substances 0.000 claims abstract description 9
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 125000005496 phosphonium group Chemical group 0.000 claims abstract description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 5
- 150000003573 thiols Chemical class 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 4
- 229910004727 OSO3H Inorganic materials 0.000 claims abstract 4
- 229910006069 SO3H Inorganic materials 0.000 claims abstract 4
- 239000000203 mixture Substances 0.000 claims description 33
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 1
- -1 phenyl boronic acid compound Chemical class 0.000 abstract description 25
- HXITXNWTGFUOAU-UHFFFAOYSA-N dihydroxy-phenylborane Natural products OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 abstract description 20
- 102100036378 T-cell immunomodulatory protein Human genes 0.000 abstract 1
- 101710194900 T-cell immunomodulatory protein Proteins 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 33
- 238000003786 synthesis reaction Methods 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- 229920000642 polymer Polymers 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 102000004882 Lipase Human genes 0.000 description 14
- 108090001060 Lipase Proteins 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 12
- 239000004367 Lipase Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 235000019421 lipase Nutrition 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 229940127470 Lipase Inhibitors Drugs 0.000 description 10
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 10
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 10
- 229940117969 neopentyl glycol Drugs 0.000 description 10
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229940040461 lipase Drugs 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- JPTNTBSBJPCXGI-UHFFFAOYSA-N 1-(4-bromo-2,5-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Br)C=C1F JPTNTBSBJPCXGI-UHFFFAOYSA-N 0.000 description 5
- 229940086609 Lipase inhibitor Drugs 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000005620 boronic acid group Chemical group 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 150000003626 triacylglycerols Chemical class 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- GVXYQPSIVLTOJD-UHFFFAOYSA-N [4-(2-bromoacetyl)-2,5-difluorophenyl]boronic acid Chemical compound OB(O)C1=CC(F)=C(C(=O)CBr)C=C1F GVXYQPSIVLTOJD-UHFFFAOYSA-N 0.000 description 4
- 230000009102 absorption Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 150000001642 boronic acid derivatives Chemical class 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
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- 229930195729 fatty acid Natural products 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
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- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000013585 weight reducing agent Substances 0.000 description 4
- ULGGZAVAARQJCS-UHFFFAOYSA-N 11-sulfanylundecan-1-ol Chemical compound OCCCCCCCCCCCS ULGGZAVAARQJCS-UHFFFAOYSA-N 0.000 description 3
- QJJKXFKEZBWZHN-UHFFFAOYSA-N B1OSO1 Chemical compound B1OSO1 QJJKXFKEZBWZHN-UHFFFAOYSA-N 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- BXVHKBNJUHSCRF-UHFFFAOYSA-N [4-(2-bromoacetyl)-3-fluorophenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(=O)CBr)C(F)=C1 BXVHKBNJUHSCRF-UHFFFAOYSA-N 0.000 description 3
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- 244000215068 Acacia senegal Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
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- BQZTUNUYGFMPBU-UHFFFAOYSA-N [4-(2-bromoacetyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(=O)CBr)C=C1 BQZTUNUYGFMPBU-UHFFFAOYSA-N 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30208101P | 2001-06-29 | 2001-06-29 | |
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| PCT/US2002/020923 WO2003002570A1 (en) | 2001-06-29 | 2002-07-01 | Aryl boronic acids for treating obesity |
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| WO (1) | WO2003002570A1 (https=) |
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| US8546617B1 (en) | 2012-03-23 | 2013-10-01 | Empire Technology Development Llc | Dioxaborinanes and uses thereof |
| IN2015DN00805A (https=) * | 2012-07-31 | 2015-07-03 | Empire Technology Dev Llc | |
| US9120938B2 (en) | 2012-07-31 | 2015-09-01 | Empire Technology Development Llc | Polymerizable organoboron alkyd resin anti fouling coatings |
| ES2618374T3 (es) * | 2012-10-17 | 2017-06-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Composiciones y métodos para mejorar la absorción de glucosa |
| WO2014134716A1 (en) | 2013-03-08 | 2014-09-12 | The University Of British Columbia | Substituted organofluoroborates as imaging agents |
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| CN106243343B (zh) * | 2016-08-11 | 2018-04-03 | 江苏大学 | 一种苯硼酸功能化嵌段聚合物的合成及应用 |
| US12427209B2 (en) | 2018-12-18 | 2025-09-30 | Provincial Health Services Authority | Dual mode 18F-labelled theranostic compounds and uses thereof |
| TW202304469A (zh) * | 2021-03-24 | 2023-02-01 | 美商杜夫特學院信託管理公司 | 酸化合物、組合物及方法 |
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-
2002
- 2002-06-27 US US10/187,397 patent/US6858592B2/en not_active Expired - Lifetime
- 2002-07-01 AU AU2002316499A patent/AU2002316499B2/en not_active Ceased
- 2002-07-01 JP JP2003508951A patent/JP2004535452A/ja active Pending
- 2002-07-01 CA CA002489681A patent/CA2489681A1/en not_active Abandoned
- 2002-07-01 AT AT02746808T patent/ATE339426T1/de not_active IP Right Cessation
- 2002-07-01 PT PT02746808T patent/PT1404685E/pt unknown
- 2002-07-01 WO PCT/US2002/020923 patent/WO2003002570A1/en not_active Ceased
- 2002-07-01 DE DE60214713T patent/DE60214713T2/de not_active Expired - Fee Related
- 2002-07-01 ES ES02746808T patent/ES2275888T3/es not_active Expired - Lifetime
- 2002-07-01 EP EP02746808A patent/EP1404685B1/en not_active Expired - Lifetime
- 2002-07-01 DK DK02746808T patent/DK1404685T3/da active
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2004
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2005
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2006
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- 2006-12-05 CY CY20061101748T patent/CY1105829T1/el unknown
Also Published As
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|---|---|
| WO2003002570A1 (en) | 2003-01-09 |
| ES2275888T3 (es) | 2007-06-16 |
| US7456156B2 (en) | 2008-11-25 |
| US20030064963A1 (en) | 2003-04-03 |
| DE60214713D1 (de) | 2006-10-26 |
| US20060128664A1 (en) | 2006-06-15 |
| US7049304B2 (en) | 2006-05-23 |
| JP2004535452A (ja) | 2004-11-25 |
| CY1105829T1 (el) | 2011-02-02 |
| EP1404685B1 (en) | 2006-09-13 |
| AU2002316499B2 (en) | 2005-08-04 |
| US6858592B2 (en) | 2005-02-22 |
| AU2005220192A1 (en) | 2005-12-01 |
| PT1404685E (pt) | 2007-01-31 |
| HK1065046A1 (en) | 2005-02-08 |
| DK1404685T3 (da) | 2007-01-22 |
| ATE339426T1 (de) | 2006-10-15 |
| EP1404685A1 (en) | 2004-04-07 |
| US20050107336A1 (en) | 2005-05-19 |
| DE60214713T2 (de) | 2007-09-06 |
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