JP5138585B2 - Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン - Google Patents
Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン Download PDFInfo
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- JP5138585B2 JP5138585B2 JP2008510307A JP2008510307A JP5138585B2 JP 5138585 B2 JP5138585 B2 JP 5138585B2 JP 2008510307 A JP2008510307 A JP 2008510307A JP 2008510307 A JP2008510307 A JP 2008510307A JP 5138585 B2 JP5138585 B2 JP 5138585B2
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- Prior art keywords
- methyl
- compound
- benzyl
- mmol
- cyclopropyl
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- 238000011282 treatment Methods 0.000 title abstract description 7
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 title abstract description 4
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 92
- -1 CH 2 CF 3 Chemical group 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 35
- 229910052801 chlorine Inorganic materials 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 6
- 238000006467 substitution reaction Methods 0.000 claims 4
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- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
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- 125000005843 halogen group Chemical group 0.000 claims 1
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- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108700019146 Transgenes Proteins 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
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process 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
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- 210000004970 cd4 cell Anatomy 0.000 description 1
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- 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
- 238000011097 chromatography purification Methods 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
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 101150030339 env gene 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
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000002955 isolation Methods 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- AWKNYHJJWNMWKT-LHBLNFFHSA-N n'-[1-benzyl-4-[(e)-2-(dimethylamino)ethenyl]-5-nitro-6-oxopyrimidin-2-yl]-n,n-dimethylmethanimidamide Chemical compound O=C1C([N+]([O-])=O)=C(/C=C/N(C)C)N=C(\N=C\N(C)C)N1CC1=CC=CC=C1 AWKNYHJJWNMWKT-LHBLNFFHSA-N 0.000 description 1
- QGBYKQVZQLYYQT-UHFFFAOYSA-N n-benzyl-4-chloro-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound N=1C=2NC=CC=2C(Cl)=NC=1NCC1=CC=CC=C1 QGBYKQVZQLYYQT-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
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000002062 proliferating effect Effects 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
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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- 230000026683 transduction Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000010792 warming 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)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (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 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012143245A Division JP2012188454A (ja) | 2005-05-05 | 2012-06-26 | Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008540454A JP2008540454A (ja) | 2008-11-20 |
| JP2008540454A5 JP2008540454A5 (enExample) | 2010-05-06 |
| JP5138585B2 true JP5138585B2 (ja) | 2013-02-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| JP2012143245A Pending JP2012188454A (ja) | 2005-05-05 | 2012-06-26 | Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012143245A Pending JP2012188454A (ja) | 2005-05-05 | 2012-06-26 | Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン |
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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012188454A (ja) * | 2005-05-05 | 2012-10-04 | Ardea Biosciences Inc | Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2361835T3 (es) * | 2003-09-25 | 2011-06-22 | Janssen Pharmaceutica Nv | Derivados de purina inhibidores de la replicación del hiv. |
| CN101611035A (zh) * | 2006-12-28 | 2009-12-23 | 大正制药株式会社 | 吡唑并嘧啶化合物 |
| EP2220091B1 (en) | 2007-12-14 | 2012-07-25 | Ardea Biosciences, Inc. | Reverse transcriptase inhibitors |
| UY31631A1 (es) | 2008-02-06 | 2009-09-30 | Nuevos derivados de 7-fenil-7h-pirrolo-[2,3d]-pirimidin-2-il-amino, sales de los mismos, procesos para su preparacion, composiciones farmacéuticas que los comprenden y aplicaciones | |
| WO2010111406A2 (en) * | 2009-03-24 | 2010-09-30 | Myriad Pharmaceuticals, Inc. | Compounds and therapeutic uses thereof |
| MX392130B (es) * | 2013-06-27 | 2025-03-21 | Janssen Sciences Ireland Uc | Derivados de pirrolo[3,2-d]pirimidina para el tratamiento de infecciones víricas y otras enfermedades. |
| SG11201607990QA (en) | 2014-04-25 | 2016-11-29 | Pfizer | Heteroaromatic compounds and their use as dopamine d1 ligands |
| US10913744B2 (en) | 2015-02-13 | 2021-02-09 | Dana-Farber Cancer Institute, Inc. | LRRK2 inhibitors and methods of making and using the same |
| 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 |
| KR102048719B1 (ko) * | 2015-08-13 | 2019-11-26 | 베이징 한미 파마슈티컬 컴퍼니 리미티드 | Irak4억제제 및 이의 용도 |
| 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 |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 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 |
| EP4251613A4 (en) * | 2020-11-27 | 2024-11-20 | Allorion Therapeutics Inc. | AMINOHETEROARYL KINASE INHIBITORS |
| EP4707277A1 (en) * | 2023-05-04 | 2026-03-11 | Daewoong Pharmaceutical Co., Ltd. | Novel heterocyclic amine derivatives and pharmaceutical composition comprising same |
| 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 |
| CA2349904A1 (en) | 1998-11-12 | 2000-05-18 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods relating thereto |
| US6414147B1 (en) * | 1998-12-23 | 2002-07-02 | 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 |
| EP1597237B1 (en) | 2003-02-07 | 2016-07-27 | Janssen Pharmaceutica NV | Pyrimidine derivatives for the prevention of HIV infection |
| ES2361835T3 (es) * | 2003-09-25 | 2011-06-22 | Janssen Pharmaceutica Nv | Derivados de purina inhibidores de la replicación del hiv. |
| BRPI0517272A (pt) | 2004-10-29 | 2008-10-07 | Tibotec Pharm Ltd | derivados de pirimidina bicìclicos de inibição de hiv |
| ATE541848T1 (de) * | 2005-05-05 | 2012-02-15 | Ardea Biosciences Inc | Diaryl-purin, azapurine und deazapurine als nichtnukleoside reverse-transkriptase-inhibitoren zur behandlung von hiv |
-
2006
- 2006-05-05 AT AT06759292T patent/ATE541848T1/de active
- 2006-05-05 CN CN2006800243079A patent/CN101233135B/zh not_active Expired - Fee Related
- 2006-05-05 US US11/919,786 patent/US8227601B2/en not_active Expired - Fee Related
- 2006-05-05 EP EP06759292A patent/EP1877411B9/en not_active Expired - Lifetime
- 2006-05-05 AU AU2006244195A patent/AU2006244195B2/en not_active Ceased
- 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 ES ES06759292T patent/ES2380951T3/es not_active Expired - Lifetime
- 2006-05-05 BR BRPI0611455-5A patent/BRPI0611455A2/pt not_active Application Discontinuation
- 2006-05-05 WO PCT/US2006/017677 patent/WO2006122003A2/en not_active Ceased
- 2006-05-05 CA CA2607021A patent/CA2607021C/en 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
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012188454A (ja) * | 2005-05-05 | 2012-10-04 | Ardea Biosciences Inc | Ｈｉｖの処置のための非ヌクレオシド逆転写酵素インヒビターとしてのジアリル−プリン、−アザプリンおよび−デアザプリン |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2607021A1 (en) | 2006-11-16 |
| BRPI0611455A2 (pt) | 2010-09-08 |
| MX2007013715A (es) | 2008-01-28 |
| WO2006122003A3 (en) | 2007-01-04 |
| US8354532B2 (en) | 2013-01-15 |
| EP1877411B9 (en) | 2012-08-29 |
| JP2012188454A (ja) | 2012-10-04 |
| WO2006122003A2 (en) | 2006-11-16 |
| ZA200709481B (en) | 2008-11-26 |
| CN101233135A (zh) | 2008-07-30 |
| ATE541848T1 (de) | 2012-02-15 |
| US8227601B2 (en) | 2012-07-24 |
| ES2380951T3 (es) | 2012-05-21 |
| AU2006244195A1 (en) | 2006-11-16 |
| US20120226037A1 (en) | 2012-09-06 |
| ES2380951T9 (es) | 2012-12-21 |
| EP1877411B1 (en) | 2012-01-18 |
| CN101233135B (zh) | 2012-10-03 |
| EP1877411A2 (en) | 2008-01-16 |
| AU2006244195B2 (en) | 2012-03-15 |
| US20090124802A1 (en) | 2009-05-14 |
| EP1877411A4 (en) | 2008-10-22 |
| CA2607021C (en) | 2013-10-29 |
| JP2008540454A (ja) | 2008-11-20 |
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