ZA200600154B - Spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin-2'-one] derivatives with affinity to the alpha 7 nicotinic acetylcholine receptor - Google Patents
Spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin-2'-one] derivatives with affinity to the alpha 7 nicotinic acetylcholine receptor Download PDFInfo
- Publication number
- ZA200600154B ZA200600154B ZA200600154A ZA200600154A ZA200600154B ZA 200600154 B ZA200600154 B ZA 200600154B ZA 200600154 A ZA200600154 A ZA 200600154A ZA 200600154 A ZA200600154 A ZA 200600154A ZA 200600154 B ZA200600154 B ZA 200600154B
- Authority
- ZA
- South Africa
- Prior art keywords
- azabicyclo
- spiro
- octan
- oxazolidin
- thiophen
- Prior art date
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- 125000004122 cyclic group Chemical group 0.000 claims description 37
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- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
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- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
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- SMHKVSJKDIFJHN-GOSISDBHSA-N (5r)-3-(5-pyridin-4-ylthiophen-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound C([C@@]1(OC2=O)C3CCN(CC3)C1)N2C(S1)=CC=C1C1=CC=NC=C1 SMHKVSJKDIFJHN-GOSISDBHSA-N 0.000 description 1
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- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- ICXXXLGATNSZAV-UHFFFAOYSA-N butylazanium;chloride Chemical compound [Cl-].CCCC[NH3+] ICXXXLGATNSZAV-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
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- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
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- 239000008298 dragée Substances 0.000 description 1
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- 125000004185 ester group Chemical group 0.000 description 1
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- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
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- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
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- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 238000006263 metalation reaction Methods 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 150000002816 nickel compounds Chemical class 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000005586 smoking cessation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- 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
- C07D498/12—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 three hetero rings
- C07D498/20—Spiro-condensed systems
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- A—HUMAN NECESSITIES
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- Veterinary Medicine (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US48552303P | 2003-07-08 | 2003-07-08 |
Publications (1)
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| JP (1) | JP2007516200A (https=) |
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| KR20070090922A (ko) * | 2004-12-15 | 2007-09-06 | 아스트라제네카 아베 | 니코틴성 아세틸콜린 수용체 리간드 |
| US7649007B2 (en) | 2006-08-15 | 2010-01-19 | Wyeth Llc | Oxazolidine derivatives as PR modulators |
| TW200815428A (en) | 2006-08-15 | 2008-04-01 | Wyeth Corp | Oxazolidone derivatives as PR modulators |
| US7618989B2 (en) | 2006-08-15 | 2009-11-17 | Wyeth | Tricyclic oxazolidone derivatives useful as PR modulators |
| WO2008021309A1 (en) | 2006-08-15 | 2008-02-21 | Wyeth | Imidazolidin-2-one derivatives useful as pr modulators |
| WO2008021337A1 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Oxazinan-2-one derivatives useful as pr modulators |
| JP2010505844A (ja) * | 2006-10-03 | 2010-02-25 | ガレオン・フアーマシユーチカルズ・インコーポレーテツド | Ｓ−ニトロソチオール化合物および関連誘導体 |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| US7863291B2 (en) * | 2008-04-23 | 2011-01-04 | Bristol-Myers Squibb Company | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| US8309577B2 (en) | 2008-04-23 | 2012-11-13 | Bristol-Myers Squibb Company | Quinuclidine compounds as α-7 nicotinic acetylcholine receptor ligands |
| EP2586311B1 (de) * | 2008-07-17 | 2016-12-14 | Bayer CropScience AG | Heterocyclische Verbindungen als Schädlingsbekämpfungsmittel |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| UA107791C2 (en) * | 2009-05-05 | 2015-02-25 | Dow Agrosciences Llc | Pesticidal compositions |
| US8759550B2 (en) | 2009-08-27 | 2014-06-24 | Yeda Research And Development Co. Ltd. | Oligo- and polyfurans, preparation and uses thereof |
| US8278320B2 (en) | 2009-10-28 | 2012-10-02 | Bristol-Myers Squibb Company | Azabicyclo[2.2.1]heptane compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| US8507516B2 (en) | 2009-10-28 | 2013-08-13 | Bristol-Myers Squibb Company | Azabicyclic compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| EP2558458B1 (de) | 2010-04-16 | 2017-09-06 | Bayer Intellectual Property GmbH | Neue heterocyclische verbindungen als schädlingsbekämpfungsmittel |
| CN103025744A (zh) | 2010-04-30 | 2013-04-03 | 百时美施贵宝公司 | 作为α-7烟碱乙酰胆碱受体配体前药的氮杂二环胺N-氧化物化合物 |
| EP2595983A1 (en) | 2010-07-22 | 2013-05-29 | Novartis AG | 2,3,5-trisubstituted thiophene compounds and uses thereof |
| WO2012052412A1 (de) | 2010-10-22 | 2012-04-26 | Bayer Cropscience Ag | Neue heterocylische verbindungen als schädlingsbekämpfungsmittel |
| KR20140138293A (ko) | 2012-03-16 | 2014-12-03 | 액시킨 파마수티컬스 인코포레이티드 | 3,5-다이아미노피라졸 키나아제 억제제 |
| CN104884449A (zh) | 2012-10-31 | 2015-09-02 | 拜尔农作物科学股份公司 | 作为害虫防治剂的新的杂环化合物 |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| US9546163B2 (en) | 2014-12-23 | 2017-01-17 | Axikin Pharmaceuticals, Inc. | 3,5-diaminopyrazole kinase inhibitors |
| EA202092441A1 (ru) | 2016-06-07 | 2021-05-21 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| KR20240026521A (ko) | 2017-03-23 | 2024-02-28 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| CN112839935A (zh) | 2018-09-26 | 2021-05-25 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
Family Cites Families (3)
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| US4855290A (en) * | 1985-05-10 | 1989-08-08 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
| JP3708962B2 (ja) * | 1994-08-24 | 2005-10-19 | アストラゼネカ・アクチエボラーグ | 治療に有用なスピロ−アザ二環式化合物 |
| WO2001066546A1 (en) * | 2000-03-09 | 2001-09-13 | Mitsubishi Pharma Corporation | Spiro compounds, process for preparing the same and use thereof as drugs |
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2004
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- 2004-07-06 BR BRPI0412382-4A patent/BRPI0412382A/pt not_active IP Right Cessation
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- 2004-07-06 US US10/563,271 patent/US7514567B2/en not_active Expired - Fee Related
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| AU2004255920A1 (en) | 2005-01-20 |
| JP2007516200A (ja) | 2007-06-21 |
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| IL172762A0 (en) | 2006-04-10 |
| WO2005005435A1 (en) | 2005-01-20 |
| NO20060612L (no) | 2006-04-06 |
| TW200524942A (en) | 2005-08-01 |
| AR045040A1 (es) | 2005-10-12 |
| MXPA06000231A (es) | 2006-04-11 |
| SA04250212B1 (ar) | 2009-08-11 |
| NZ545132A (en) | 2009-07-31 |
| CA2531510A1 (en) | 2005-01-20 |
| US20060154945A1 (en) | 2006-07-13 |
| US7514567B2 (en) | 2009-04-07 |
| EP1654264A1 (en) | 2006-05-10 |
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