CA2607021C - Diaryl-purines, -azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv - Google Patents
Diaryl-purines, -azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv Download PDFInfo
- Publication number
- CA2607021C CA2607021C CA2607021A CA2607021A CA2607021C CA 2607021 C CA2607021 C CA 2607021C CA 2607021 A CA2607021 A CA 2607021A CA 2607021 A CA2607021 A CA 2607021A CA 2607021 C CA2607021 C CA 2607021C
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- Prior art keywords
- phenyl
- chcn
- cyclopropyl
- benzyl
- methyl
- Prior art date
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- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 title abstract description 4
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- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 295
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- -1 cyanomethyl Chemical group 0.000 claims description 260
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 42
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 22
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- RBSYLSXEEHXLLD-UHFFFAOYSA-N 4-[[5-methyl-4-(2,4,6-trimethylphenoxy)pyrrolo[3,2-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC2=C1N(C)C=C2 RBSYLSXEEHXLLD-UHFFFAOYSA-N 0.000 description 1
- BMKMMXFYTPSPBP-UHFFFAOYSA-N 4-[[7-bromo-4-(2,4,6-trimethylphenyl)sulfanyl-5h-pyrrolo[3,2-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C)=CC(C)=C1SC1=NC(NC=2C=CC(=CC=2)C#N)=NC2=C1NC=C2Br BMKMMXFYTPSPBP-UHFFFAOYSA-N 0.000 description 1
- LGDJXIBCBWSVIG-UHFFFAOYSA-N 4-[[7-chloro-2-(4-cyanoanilino)-5h-pyrrolo[3,2-d]pyrimidin-4-yl]oxy]-3,5-dimethylbenzonitrile Chemical compound CC1=CC(C#N)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC2=C1NC=C2Cl LGDJXIBCBWSVIG-UHFFFAOYSA-N 0.000 description 1
- LVJFMAWBKAXDCF-UHFFFAOYSA-N 4-[[7-chloro-5-methyl-4-(2,4,6-trimethylphenoxy)pyrrolo[3,2-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC2=C1N(C)C=C2Cl LVJFMAWBKAXDCF-UHFFFAOYSA-N 0.000 description 1
- FKBFZTVMDGNMTH-UHFFFAOYSA-N 7-benzyl-4-n-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidine-2,4-diamine Chemical compound CC1=CC(C)=CC(C)=C1NC1=NC(N)=NC2=C1C=CN2CC1=CC=CC=C1 FKBFZTVMDGNMTH-UHFFFAOYSA-N 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- 241001275944 Misgurnus anguillicaudatus Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- GFRROZIJVHUSKZ-FXGMSQOLSA-N OS I Natural products C[C@@H]1O[C@@H](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](OC[C@@H](O)[C@@H](O)[C@@H](O)CO)[C@@H]2NC(=O)C)[C@H](O)[C@H](O)[C@H]1O GFRROZIJVHUSKZ-FXGMSQOLSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101150104269 RT gene Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 239000011717 all-trans-retinol Substances 0.000 description 1
- 235000019169 all-trans-retinol Nutrition 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- YQXCVAGCMNFUMQ-UHFFFAOYSA-N capravirine Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC1=C(C(C)C)N=C(COC(N)=O)N1CC1=CC=NC=C1 YQXCVAGCMNFUMQ-UHFFFAOYSA-N 0.000 description 1
- 229950008230 capravirine Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- BYIHXUHOYZDNTR-UHFFFAOYSA-M chlorozinc(1+);cyclopropane Chemical compound [Cl-].[Zn+2].C1C[CH-]1 BYIHXUHOYZDNTR-UHFFFAOYSA-M 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000000716 hydrazinylidene group Chemical group [*]=NN([H])[H] 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- DSWNRHCOGVRDOE-UHFFFAOYSA-N n,n-dimethylmethanimidamide Chemical compound CN(C)C=N DSWNRHCOGVRDOE-UHFFFAOYSA-N 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67866705P | 2005-05-05 | 2005-05-05 | |
| US60/678,667 | 2005-05-05 | ||
| PCT/US2006/017677 WO2006122003A2 (en) | 2005-05-05 | 2006-05-05 | Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2607021A1 CA2607021A1 (en) | 2006-11-16 |
| CA2607021C true CA2607021C (en) | 2013-10-29 |
Family
ID=37397195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2607021A Expired - Fee Related CA2607021C (en) | 2005-05-05 | 2006-05-05 | Diaryl-purines, -azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US8227601B2 (enExample) |
| EP (1) | EP1877411B9 (enExample) |
| JP (2) | JP5138585B2 (enExample) |
| CN (1) | CN101233135B (enExample) |
| AT (1) | ATE541848T1 (enExample) |
| AU (1) | AU2006244195B2 (enExample) |
| BR (1) | BRPI0611455A2 (enExample) |
| CA (1) | CA2607021C (enExample) |
| ES (1) | ES2380951T3 (enExample) |
| MX (1) | MX2007013715A (enExample) |
| WO (1) | WO2006122003A2 (enExample) |
| ZA (1) | ZA200709481B (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0414791A (pt) * | 2003-09-25 | 2006-11-21 | Janssen Pharmaceutica Nv | derivados de purina inibidores da replicação do hiv |
| ES2380951T3 (es) * | 2005-05-05 | 2012-05-21 | Ardea Biosciences, Inc. | Diaril-purinas, -azapurinasy - desazapurinas como inhibidores no nucleósidos de la transcriptasa inversa para el tratamiento del VIH |
| KR20090103897A (ko) * | 2006-12-28 | 2009-10-01 | 다이쇼 세이야꾸 가부시끼가이샤 | 피라졸로피리미딘 화합물 |
| WO2009079412A2 (en) | 2007-12-14 | 2009-06-25 | Ardea Biosciences Inc. | Reverse transcriptase inhibitors |
| PE20091485A1 (es) | 2008-02-06 | 2009-10-26 | Novartis Ag | DERIVADOS DE PIRROLO-[2,3-d]-PIRIMIDINA COMO INHIBIDORES DE CINASAS |
| WO2010111406A2 (en) * | 2009-03-24 | 2010-09-30 | Myriad Pharmaceuticals, Inc. | Compounds and therapeutic uses thereof |
| NO3030563T3 (enExample) * | 2013-06-27 | 2018-01-06 | ||
| CN106232118A (zh) | 2014-04-25 | 2016-12-14 | 辉瑞大药厂 | 杂芳族化合物及其作为多巴胺d1配体的用途 |
| EP3256475A4 (en) | 2015-02-13 | 2019-02-13 | Dana-Farber Cancer Institute, Inc. | LRRK2 INHIBITORS AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| CN106188060A (zh) * | 2015-04-29 | 2016-12-07 | 厦门大学 | 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用 |
| JP6541871B2 (ja) * | 2015-08-13 | 2019-07-10 | 北京韓美薬品有限公司 | Ｉｒａｋ４阻害剤、及びその応用 |
| CN106117242B (zh) * | 2016-06-27 | 2018-08-03 | 山东大学 | 四氢噻喃并嘧啶类衍生物及其制备方法与应用 |
| CN107793417B (zh) * | 2016-09-05 | 2020-06-09 | 复旦大学 | 吡咯并[2,3-d]嘧啶类化合物及其盐，及制备方法和药用用途 |
| CN106749266B (zh) * | 2016-11-14 | 2019-01-22 | 山东大学 | 吡咯并[2,3-d]嘧啶类化合物的高效制备方法 |
| TW201945003A (zh) | 2018-03-01 | 2019-12-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | ２，４－二胺基喹唑啉衍生物及其醫學用途 |
| CN111499639B (zh) * | 2019-01-31 | 2022-03-04 | 四川大学华西医院 | 嘧啶酮衍生物及其在制药中的应用 |
| US20230279006A1 (en) * | 2020-07-08 | 2023-09-07 | Klotho Therapeutics, Inc. | Novel compounds and methods for increasing klotho gene expression |
| CN116528869A (zh) * | 2020-11-27 | 2023-08-01 | 安锐生物医药科技(广州)有限公司 | 氨基杂芳基激酶抑制剂 |
| WO2024228580A1 (ko) * | 2023-05-04 | 2024-11-07 | 주식회사 대웅제약 | 신규한 헤테로사이클릭아민 유도체 및 이를 포함하는 약학 조성물 |
| US20250333424A1 (en) * | 2024-03-01 | 2025-10-30 | Gilead Sciences, Inc. | Antiviral compounds |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ229453A (en) * | 1988-06-10 | 1991-08-27 | Univ Minnesota & Southern Rese | A pharmaceutical composition containing purine derivatives with nucleosides such as azt, as antiviral agents |
| BR9915129A (pt) | 1998-11-12 | 2001-08-07 | Neurocrine Biosciences Inc | Antagonistas do receptor de crf e processos relacionados aos mesmos |
| AU2217200A (en) * | 1998-12-23 | 2000-07-12 | Neurogen Corporation | 2-amino-9-alkylpurines: gaba brain receptor ligands |
| CZ27399A3 (cs) | 1999-01-26 | 2000-08-16 | Ústav Experimentální Botaniky Av Čr | Substituované dusíkaté heterocyklické deriváty, způsob jejich přípravy, tyto deriváty pro použití jako léčiva, farmaceutická kompozice a kombinovaný farmaceutický přípravek tyto deriváty obsahující a použití těchto derivátů pro výrobu léčiv |
| YU25500A (sh) * | 1999-05-11 | 2003-08-29 | Pfizer Products Inc. | Postupak za sintezu analoga nukleozida |
| JO3429B1 (ar) | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
| CN1747937A (zh) | 2003-02-07 | 2006-03-15 | 詹森药业有限公司 | 预防hiv感染的嘧啶衍生物 |
| BRPI0414791A (pt) * | 2003-09-25 | 2006-11-21 | Janssen Pharmaceutica Nv | derivados de purina inibidores da replicação do hiv |
| KR20070085286A (ko) | 2004-10-29 | 2007-08-27 | 티보텍 파마슈티칼즈 리미티드 | Ｈｉｖ를 저해하는 바이사이클릭 피리미딘 유도체 |
| ES2380951T3 (es) * | 2005-05-05 | 2012-05-21 | Ardea Biosciences, Inc. | Diaril-purinas, -azapurinasy - desazapurinas como inhibidores no nucleósidos de la transcriptasa inversa para el tratamiento del VIH |
-
2006
- 2006-05-05 ES ES06759292T patent/ES2380951T3/es active Active
- 2006-05-05 CA CA2607021A patent/CA2607021C/en not_active Expired - Fee Related
- 2006-05-05 AT AT06759292T patent/ATE541848T1/de active
- 2006-05-05 WO PCT/US2006/017677 patent/WO2006122003A2/en not_active Ceased
- 2006-05-05 EP EP06759292A patent/EP1877411B9/en not_active Not-in-force
- 2006-05-05 AU AU2006244195A patent/AU2006244195B2/en not_active Ceased
- 2006-05-05 BR BRPI0611455-5A patent/BRPI0611455A2/pt not_active Application Discontinuation
- 2006-05-05 MX MX2007013715A patent/MX2007013715A/es active IP Right Grant
- 2006-05-05 JP JP2008510307A patent/JP5138585B2/ja not_active Expired - Fee Related
- 2006-05-05 US US11/919,786 patent/US8227601B2/en not_active Expired - Fee Related
- 2006-05-05 CN CN2006800243079A patent/CN101233135B/zh not_active Expired - Fee Related
-
2007
- 2007-11-02 ZA ZA200709481A patent/ZA200709481B/xx unknown
-
2012
- 2012-05-11 US US13/470,116 patent/US8354532B2/en not_active Expired - Fee Related
- 2012-06-26 JP JP2012143245A patent/JP2012188454A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1877411A4 (en) | 2008-10-22 |
| CN101233135A (zh) | 2008-07-30 |
| EP1877411A2 (en) | 2008-01-16 |
| CN101233135B (zh) | 2012-10-03 |
| WO2006122003A2 (en) | 2006-11-16 |
| MX2007013715A (es) | 2008-01-28 |
| CA2607021A1 (en) | 2006-11-16 |
| EP1877411B9 (en) | 2012-08-29 |
| US8227601B2 (en) | 2012-07-24 |
| BRPI0611455A2 (pt) | 2010-09-08 |
| JP2008540454A (ja) | 2008-11-20 |
| JP2012188454A (ja) | 2012-10-04 |
| ES2380951T3 (es) | 2012-05-21 |
| JP5138585B2 (ja) | 2013-02-06 |
| ES2380951T9 (es) | 2012-12-21 |
| US8354532B2 (en) | 2013-01-15 |
| AU2006244195B2 (en) | 2012-03-15 |
| ZA200709481B (en) | 2008-11-26 |
| WO2006122003A3 (en) | 2007-01-04 |
| US20120226037A1 (en) | 2012-09-06 |
| EP1877411B1 (en) | 2012-01-18 |
| ATE541848T1 (de) | 2012-02-15 |
| AU2006244195A1 (en) | 2006-11-16 |
| US20090124802A1 (en) | 2009-05-14 |
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