JP2008514611A - Ｃ型肝炎ウイルスによる感染を処置するためのカルバゾールおよびシクロペンタインドールの誘導体 - Google Patents
Ｃ型肝炎ウイルスによる感染を処置するためのカルバゾールおよびシクロペンタインドールの誘導体 Download PDFInfo
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- JP2008514611A JP2008514611A JP2007533604A JP2007533604A JP2008514611A JP 2008514611 A JP2008514611 A JP 2008514611A JP 2007533604 A JP2007533604 A JP 2007533604A JP 2007533604 A JP2007533604 A JP 2007533604A JP 2008514611 A JP2008514611 A JP 2008514611A
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- carbon atoms
- tetrahydro
- carboxylic acid
- indole
- cyclopenta
- Prior art date
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- 208000015181 infectious disease Diseases 0.000 title claims description 5
- 241000711549 Hepacivirus C Species 0.000 title description 20
- HFGUJIUXLNDRAF-UHFFFAOYSA-N cyclopenta[g]indole Chemical compound C1=CC2=CC=CC2=C2N=CC=C21 HFGUJIUXLNDRAF-UHFFFAOYSA-N 0.000 title description 6
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- 238000000034 method Methods 0.000 claims abstract description 26
- 208000010710 hepatitis C virus infection Diseases 0.000 claims abstract description 9
- 241000124008 Mammalia Species 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 170
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- -1 furanylmethyl Chemical group 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 210000004027 cell Anatomy 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 208000005176 Hepatitis C Diseases 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- UVKVBHPKFLJUCF-UHFFFAOYSA-N 5,8-dichloro-3-prop-2-enyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(Cl)=C2C2=C1C(C(=O)O)(CC=C)CC2 UVKVBHPKFLJUCF-UHFFFAOYSA-N 0.000 claims description 7
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- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
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- AFDTUDKFSMWIAU-UHFFFAOYSA-N 2-(5,7-difluoro-1-propyl-2,3,4,9-tetrahydrocarbazol-1-yl)acetic acid Chemical compound N1C2=CC(F)=CC(F)=C2C2=C1C(CCC)(CC(O)=O)CCC2 AFDTUDKFSMWIAU-UHFFFAOYSA-N 0.000 claims description 4
- KKRITWOLVWDFFN-UHFFFAOYSA-N 2-(5,8-dicyano-1-propyl-2,3,4,9-tetrahydrocarbazol-1-yl)acetic acid Chemical compound N1C2=C(C#N)C=CC(C#N)=C2C2=C1C(CCC)(CC(O)=O)CCC2 KKRITWOLVWDFFN-UHFFFAOYSA-N 0.000 claims description 4
- NQNDJICKBDRTND-UHFFFAOYSA-N 2-(5-cyano-8-fluoro-1-propyl-2,3,4,9-tetrahydrocarbazol-1-yl)acetic acid Chemical compound N1C2=C(F)C=CC(C#N)=C2C2=C1C(CCC)(CC(O)=O)CCC2 NQNDJICKBDRTND-UHFFFAOYSA-N 0.000 claims description 4
- SGWDODVGBXFOHX-UHFFFAOYSA-N 2-(8-carbamoyl-5-cyano-1-propyl-2,3,4,9-tetrahydrocarbazol-1-yl)acetic acid Chemical compound N1C2=C(C(N)=O)C=CC(C#N)=C2C2=C1C(CCC)(CC(O)=O)CCC2 SGWDODVGBXFOHX-UHFFFAOYSA-N 0.000 claims description 4
- NDKUXQXILLYKKZ-UHFFFAOYSA-N 3-butyl-5,8-dichloro-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(Cl)=C2C2=C1C(CCCC)(C(O)=O)CC2 NDKUXQXILLYKKZ-UHFFFAOYSA-N 0.000 claims description 4
- VUCHCGKNUOLUQK-UHFFFAOYSA-N 3-butyl-7-fluoro-5-methyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=C(F)C=C2C2=C1C(CCCC)(C(O)=O)CC2 VUCHCGKNUOLUQK-UHFFFAOYSA-N 0.000 claims description 4
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- VQOPOVBNNLJNSI-UHFFFAOYSA-N 3-butyl-8-cyano-5-methyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=CC(C#N)=C2C2=C1C(CCCC)(C(O)=O)CC2 VQOPOVBNNLJNSI-UHFFFAOYSA-N 0.000 claims description 4
- PJCITKIXTABVGF-UHFFFAOYSA-N 3-butyl-8-cyano-7-fluoro-5-methyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=C(F)C(C#N)=C2C2=C1C(CCCC)(C(O)=O)CC2 PJCITKIXTABVGF-UHFFFAOYSA-N 0.000 claims description 4
- TVSMABGYTPMGPU-UHFFFAOYSA-N 5,8-dichloro-1-ethyl-2,3,4,9-tetrahydrocarbazole-1-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(Cl)=C2C2=C1C(CC)(C(O)=O)CCC2 TVSMABGYTPMGPU-UHFFFAOYSA-N 0.000 claims description 4
- WXVDJFVBOHMICQ-UHFFFAOYSA-N 5,8-dichloro-1-propyl-2,3,4,9-tetrahydrocarbazole-1-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(Cl)=C2C2=C1C(CCC)(C(O)=O)CCC2 WXVDJFVBOHMICQ-UHFFFAOYSA-N 0.000 claims description 4
- ZEBPOFKSMDBBIP-UHFFFAOYSA-N 5,8-dichloro-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(Cl)=C2C2=C1C(CCC)(C(O)=O)CC2 ZEBPOFKSMDBBIP-UHFFFAOYSA-N 0.000 claims description 4
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- KRFGICBRUITTJH-UHFFFAOYSA-N 5-cyano-8-fluoro-1-propyl-2,3,4,9-tetrahydrocarbazole-1-carboxylic acid Chemical compound N1C2=C(F)C=CC(C#N)=C2C2=C1C(CCC)(C(O)=O)CCC2 KRFGICBRUITTJH-UHFFFAOYSA-N 0.000 claims description 4
- MODPSKZFBZNESH-UHFFFAOYSA-N 5-cyano-8-methyl-1-propyl-2,3,4,9-tetrahydrocarbazole-1-carboxylic acid Chemical compound N1C2=C(C)C=CC(C#N)=C2C2=C1C(CCC)(C(O)=O)CCC2 MODPSKZFBZNESH-UHFFFAOYSA-N 0.000 claims description 4
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- BELKQACUXXVKGU-UHFFFAOYSA-N 8-bromo-3-butyl-5-methyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=CC(Br)=C2C2=C1C(CCCC)(C(O)=O)CC2 BELKQACUXXVKGU-UHFFFAOYSA-N 0.000 claims description 4
- PJSPQZHMSYHQHW-UHFFFAOYSA-N 8-bromo-3-butyl-7-fluoro-5-methyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=C(F)C(Br)=C2C2=C1C(CCCC)(C(O)=O)CC2 PJSPQZHMSYHQHW-UHFFFAOYSA-N 0.000 claims description 4
- AVGMUKWZKNEEGD-UHFFFAOYSA-N 8-bromo-5-fluoro-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(F)C=CC(Br)=C2C2=C1C(CCC)(C(O)=O)CC2 AVGMUKWZKNEEGD-UHFFFAOYSA-N 0.000 claims description 4
- YTYSTPUXYCVFKA-UHFFFAOYSA-N 8-bromo-5-methyl-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=CC(Br)=C2C2=C1C(CCC)(C(O)=O)CC2 YTYSTPUXYCVFKA-UHFFFAOYSA-N 0.000 claims description 4
- SOOIMQWGGBSTMX-UHFFFAOYSA-N 8-bromo-7-fluoro-5-methyl-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=C(F)C(Br)=C2C2=C1C(CCC)(C(O)=O)CC2 SOOIMQWGGBSTMX-UHFFFAOYSA-N 0.000 claims description 4
- UJIFIPSJPHVBSG-UHFFFAOYSA-N 8-chloro-1-propyl-5-(trifluoromethyl)-2,3,4,9-tetrahydrocarbazole-1-carboxylic acid Chemical compound N1C2=C(Cl)C=CC(C(F)(F)F)=C2C2=C1C(CCC)(C(O)=O)CCC2 UJIFIPSJPHVBSG-UHFFFAOYSA-N 0.000 claims description 4
- GBRSGCDWLVKGNZ-UHFFFAOYSA-N 8-cyano-5-fluoro-3-prop-2-enyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(F)C=CC(C#N)=C2C2=C1C(C(=O)O)(CC=C)CC2 GBRSGCDWLVKGNZ-UHFFFAOYSA-N 0.000 claims description 4
- CYFCIXPSJVHSMX-UHFFFAOYSA-N 8-cyano-5-fluoro-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(F)C=CC(C#N)=C2C2=C1C(CCC)(C(O)=O)CC2 CYFCIXPSJVHSMX-UHFFFAOYSA-N 0.000 claims description 4
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- GXCUYACJTXNSGX-UHFFFAOYSA-N 8-cyano-5-methyl-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=CC(C#N)=C2C2=C1C(CCC)(C(O)=O)CC2 GXCUYACJTXNSGX-UHFFFAOYSA-N 0.000 claims description 4
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- NNMAGWLGRCCEIE-UHFFFAOYSA-N 8-cyano-7-fluoro-5-methyl-3-propyl-2,4-dihydro-1h-cyclopenta[b]indole-3-carboxylic acid Chemical compound N1C2=C(C)C=C(F)C(C#N)=C2C2=C1C(CCC)(C(O)=O)CC2 NNMAGWLGRCCEIE-UHFFFAOYSA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
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- 210000004962 mammalian cell Anatomy 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 6
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61214404P | 2004-09-23 | 2004-09-23 | |
| PCT/US2005/033803 WO2006034337A2 (en) | 2004-09-23 | 2005-09-21 | Carbazole and cyclopentaindole derivatives to treat infection with hepatitis c virus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008514611A true JP2008514611A (ja) | 2008-05-08 |
| JP2008514611A5 JP2008514611A5 (enExample) | 2008-11-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007533604A Withdrawn JP2008514611A (ja) | 2004-09-23 | 2005-09-21 | Ｃ型肝炎ウイルスによる感染を処置するためのカルバゾールおよびシクロペンタインドールの誘導体 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7250441B2 (enExample) |
| EP (1) | EP1793819A2 (enExample) |
| JP (1) | JP2008514611A (enExample) |
| CN (1) | CN101035528A (enExample) |
| AU (1) | AU2005286727A1 (enExample) |
| BR (1) | BRPI0515596A (enExample) |
| CA (1) | CA2577413A1 (enExample) |
| MX (1) | MX2007003371A (enExample) |
| WO (1) | WO2006034337A2 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006121467A2 (en) * | 2004-11-22 | 2006-11-16 | Smithkline Beecham Corporation | Tetrahydrocarbazole derivatives for treating flaviridae viruses |
| JP2009508875A (ja) | 2005-09-19 | 2009-03-05 | エミスフェアー・テクノロジーズ・インク | Ｎ−（５−クロロサリチロイル）−８−アミノカプリル酸二ナトリウム塩の結晶形 |
| WO2008024763A2 (en) * | 2006-08-25 | 2008-02-28 | Wyeth | Identification and characterization of hcv replicon variants with reduced susceptibility to hcv-796, and methods related thereto |
| EP2081922B1 (en) | 2006-12-22 | 2012-02-01 | Schering Corporation | 5,6-Ring annulated indole derivatives and use thereof |
| AU2007339386B8 (en) | 2006-12-22 | 2013-12-05 | Merck Sharp & Dohme Corp. | 4, 5-ring annulated indole derivatives for treating or preventing of HCV and related viral infections |
| EP2064180B1 (en) | 2006-12-22 | 2016-07-13 | Merck Sharp & Dohme Corp. | 4,5-ring annulated indole derivatives for treating or preventing of hcv and related viral infections |
| JP2010526143A (ja) | 2007-05-04 | 2010-07-29 | 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 | Ｈｃｖ感染の処置のための併用療法 |
| KR20100067652A (ko) | 2007-08-29 | 2010-06-21 | 쉐링 코포레이션 | 치환된 인돌 유도체 및 이의 사용방법 |
| AU2008295483B2 (en) * | 2007-08-29 | 2013-11-21 | Merck Sharp & Dohme Corp. | Tetracyclic indole derivatives and their use for treating or preventing viral infections |
| CA2697375A1 (en) | 2007-08-29 | 2009-03-12 | Schering Corporation | 2, 3-substituted indole derivatives for treating viral infections |
| KR20100065167A (ko) | 2007-08-29 | 2010-06-15 | 쉐링 코포레이션 | 바이러스 감염 치료용 2,3-치환된 아자인돌 유도체 |
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| EP0307077A1 (en) * | 1987-07-21 | 1989-03-15 | Merck Frosst Canada Inc. | Tetrahydrocarbazoles for the improvement of cyclosporin therapy |
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| US20050256181A1 (en) * | 2004-01-29 | 2005-11-17 | Elixir Pharmaceuticals, Inc. | Treating a viral disorder |
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2005
- 2005-09-21 JP JP2007533604A patent/JP2008514611A/ja not_active Withdrawn
- 2005-09-21 CN CNA2005800316732A patent/CN101035528A/zh active Pending
- 2005-09-21 EP EP05815334A patent/EP1793819A2/en not_active Withdrawn
- 2005-09-21 CA CA002577413A patent/CA2577413A1/en not_active Abandoned
- 2005-09-21 MX MX2007003371A patent/MX2007003371A/es not_active Application Discontinuation
- 2005-09-21 WO PCT/US2005/033803 patent/WO2006034337A2/en not_active Ceased
- 2005-09-21 AU AU2005286727A patent/AU2005286727A1/en not_active Abandoned
- 2005-09-21 BR BRPI0515596-7A patent/BRPI0515596A/pt not_active IP Right Cessation
- 2005-09-21 US US11/230,729 patent/US7250441B2/en not_active Expired - Fee Related
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| EP1793819A2 (en) | 2007-06-13 |
| CA2577413A1 (en) | 2006-03-30 |
| CN101035528A (zh) | 2007-09-12 |
| WO2006034337A3 (en) | 2006-09-14 |
| WO2006034337A2 (en) | 2006-03-30 |
| US20060063821A1 (en) | 2006-03-23 |
| MX2007003371A (es) | 2007-05-07 |
| AU2005286727A1 (en) | 2006-03-30 |
| US7250441B2 (en) | 2007-07-31 |
| BRPI0515596A (pt) | 2008-07-29 |
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