CA2601996A1 - Purine derivatives as a3 and a1 adenosine receptor agonists - Google Patents
Purine derivatives as a3 and a1 adenosine receptor agonists Download PDFInfo
- Publication number
- CA2601996A1 CA2601996A1 CA002601996A CA2601996A CA2601996A1 CA 2601996 A1 CA2601996 A1 CA 2601996A1 CA 002601996 A CA002601996 A CA 002601996A CA 2601996 A CA2601996 A CA 2601996A CA 2601996 A1 CA2601996 A1 CA 2601996A1
- Authority
- CA
- Canada
- Prior art keywords
- hydroxy
- compound
- alkyl
- chloro
- hydrogen
- 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
- 101150046889 ADORA3 gene Proteins 0.000 title claims abstract description 41
- 239000003379 purinergic P1 receptor agonist Substances 0.000 title abstract description 12
- 101150007969 ADORA1 gene Proteins 0.000 title abstract description 5
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 2
- 150000003212 purines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 154
- 238000000034 method Methods 0.000 claims abstract description 62
- 239000000556 agonist Substances 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- -1 hydroxy, amino Chemical group 0.000 claims description 116
- 239000001257 hydrogen Substances 0.000 claims description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims description 89
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 88
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 66
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 60
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- 108050000203 Adenosine receptors Proteins 0.000 claims description 15
- 102000009346 Adenosine receptors Human genes 0.000 claims description 15
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000003853 4-amino-3-iodobenzyl group Chemical group [H]N([H])C1=C(I)C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- 125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 4
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006482 3-iodobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(I)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004136 7-norbornyl group Chemical group [H]C1([H])C([H])([H])C2([H])C([H])([H])C([H])([H])C1([H])C2([H])* 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 239000011737 fluorine Chemical group 0.000 claims description 3
- 229910052731 fluorine Chemical group 0.000 claims description 3
- 125000003106 haloaryl group Chemical group 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000006766 (C2-C6) alkynyloxy group Chemical group 0.000 claims description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
- 239000002777 nucleoside Substances 0.000 abstract description 12
- 238000011282 treatment Methods 0.000 abstract description 9
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- 229930024421 Adenine Natural products 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract description 2
- 229960000643 adenine Drugs 0.000 abstract description 2
- 208000006673 asthma Diseases 0.000 abstract description 2
- 230000004054 inflammatory process Effects 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 206010003119 arrhythmia Diseases 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 208000031225 myocardial ischemia Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 107
- 238000005481 NMR spectroscopy Methods 0.000 description 71
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 68
- 101150041968 CDC13 gene Proteins 0.000 description 66
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- 239000000243 solution Substances 0.000 description 48
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- 239000000203 mixture Substances 0.000 description 46
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 41
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Classifications
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- 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
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US60882304P | 2004-09-09 | 2004-09-09 | |
| US60/608,823 | 2004-09-09 | ||
| PCT/US2005/031678 WO2006031505A1 (en) | 2004-09-09 | 2005-09-02 | Purine derivatives as a3 and a1 adenosine receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2601996A1 true CA2601996A1 (en) | 2006-03-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002601996A Abandoned CA2601996A1 (en) | 2004-09-09 | 2005-09-02 | Purine derivatives as a3 and a1 adenosine receptor agonists |
Country Status (10)
| Country | Link |
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| US (1) | US7825126B2 (https=) |
| EP (1) | EP1794162A1 (https=) |
| JP (2) | JP2008512457A (https=) |
| KR (1) | KR20070050484A (https=) |
| CN (1) | CN101056879B (https=) |
| AU (1) | AU2005285284B2 (https=) |
| BR (1) | BRPI0515030A (https=) |
| CA (1) | CA2601996A1 (https=) |
| IL (1) | IL181716A0 (https=) |
| WO (1) | WO2006031505A1 (https=) |
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| EP2322525B1 (en) * | 2006-04-21 | 2013-09-18 | Novartis AG | Purine derivatives for use as adenosin A2A receptor agonists |
| WO2007139775A2 (en) * | 2006-05-23 | 2007-12-06 | University Of Connecticut | N-methanocarba derivatives to treat cardiac diseases |
| WO2008000743A2 (en) * | 2006-06-27 | 2008-01-03 | Biovitrum Ab (Publ) | Novel 2',3'-methylidene acetyl adenosine prodrugs for use as prodrugs for adenosine receptor agonists |
| EP1889846A1 (en) | 2006-07-13 | 2008-02-20 | Novartis AG | Purine derivatives as A2a agonists |
| WO2008023362A2 (en) * | 2006-08-21 | 2008-02-28 | Can-Fite Biopharma Ltd. | Use of a combination of methotrexate and an a3ar agonist for the treatment of cancer |
| EP1903044A1 (en) * | 2006-09-14 | 2008-03-26 | Novartis AG | Adenosine Derivatives as A2A Receptor Agonists |
| CA2669108A1 (en) * | 2006-11-10 | 2008-05-15 | Novartis Ag | Cyclopentene diol monoacetate derivatives |
| NZ601866A (en) | 2007-06-29 | 2013-12-20 | Acucela Inc | Alkynyl phenyl derivative compounds for treating ophthalmic diseases and disorders |
| EP2170401A1 (en) | 2007-06-29 | 2010-04-07 | Government of the United States of America, Represented by the Secretary, Department of Health and Human Services | Dendrimer conjugates of agonists and antagonists of the gpcr superfamily |
| JP5592262B2 (ja) | 2007-10-15 | 2014-09-17 | キャン−ファイト・バイオファーマ・リミテッド | 肝細胞の増殖を誘導する方法及びその使用 |
| US8916570B2 (en) | 2008-03-31 | 2014-12-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor agonists and antagonists |
| WO2010014921A2 (en) * | 2008-08-01 | 2010-02-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor antagonists and partial agonists |
| CA2720037C (en) * | 2008-03-31 | 2016-08-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Purine derivatives as a3 adenosine receptor-selective agonists |
| US9181253B2 (en) | 2008-08-01 | 2015-11-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenosine receptor agonists, partial agonists, and antagonists |
| WO2011068978A1 (en) | 2009-12-02 | 2011-06-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methanocarba adenosine derivatives and dendrimer conjugates thereof |
| ES2654363T3 (es) | 2010-02-22 | 2018-02-13 | University Of Connecticut | Derivados de AMP para tratar enfermedades cardíacas |
| WO2011123518A1 (en) | 2010-03-31 | 2011-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenosine receptor agonists for the treatment and prevention of vascular or joint capsule calcification disorders |
| WO2012100654A1 (zh) * | 2011-01-26 | 2012-08-02 | 北京化工大学 | 呋喃核糖基嘌呤类化合物及其制备方法和应用 |
| MX2021012208A (es) | 2013-10-04 | 2023-01-19 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos y usos de los mismos. |
| WO2015080940A1 (en) * | 2013-11-27 | 2015-06-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor agonists |
| NZ724368A (en) | 2014-03-19 | 2023-07-28 | Infinity Pharmaceuticals Inc | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP4585268A3 (en) | 2015-09-14 | 2025-10-15 | Twelve Therapeutics, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| KR102445887B1 (ko) * | 2016-04-21 | 2022-09-21 | 아스트로사이트 파마슈티컬스, 인코포레이티드 | 신경계 및 심혈관계 병태 치료를 위한 화합물 및 방법 |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| KR101820909B1 (ko) * | 2017-07-07 | 2018-01-23 | 퓨쳐메디신 주식회사 | 아데노신 유도체를 포함하는 만성신장질환 예방 및 치료용 약학적 조성물 |
| IL276358B2 (en) | 2018-02-09 | 2024-11-01 | Astrocyte Pharmaceuticals Inc | Compounds and methods for treating addiction and related disorders |
| EA202190576A1 (ru) | 2018-09-26 | 2021-09-03 | Астросайт Фармасьютикалс, Инк. | Полиморфные соединения и их применение |
| WO2022232810A1 (en) * | 2021-04-28 | 2022-11-03 | Astrocyte Pharmaceuticals, Inc. | Purine nucleosides, their intermediates, and methods of preparation thereof |
| US12606863B2 (en) | 2021-05-13 | 2026-04-21 | Promega Corporation | Bioluminescent detection of DNA synthesis |
| WO2025019529A1 (en) * | 2023-07-17 | 2025-01-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 5-ht 2b serotonin receptor antagonists, pharmaceutical compositions thereof, and methods of use thereof |
| CN117503766B (zh) * | 2024-01-04 | 2024-04-26 | 中国康复研究中心 | Pld抑制剂在制备治疗脊髓损伤的药物中的用途 |
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| DE69428536T2 (de) * | 1993-07-13 | 2002-06-06 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | A3 -adenosin -rezeptor agonisten |
| US5688774A (en) * | 1993-07-13 | 1997-11-18 | The United States Of America As Represented By The Department Of Health And Human Services | A3 adenosine receptor agonists |
| GB9723589D0 (en) * | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| US6586413B2 (en) * | 1999-11-05 | 2003-07-01 | The United States Of America As Represented By The Department Of Health And Human Services | Methods and compositions for reducing ischemic injury of the heart by administering adenosine receptor agonists and antagonists |
| US7087589B2 (en) * | 2000-01-14 | 2006-08-08 | The United States Of America As Represented By The Department Of Health And Human Services | Methanocarba cycloakyl nucleoside analogues |
| EP1241176A1 (en) * | 2001-03-16 | 2002-09-18 | Pfizer Products Inc. | Purine derivatives for the treatment of ischemia |
| US20050261237A1 (en) * | 2003-04-25 | 2005-11-24 | Boojamra Constantine G | Nucleoside phosphonate analogs |
| US20090192077A1 (en) * | 2005-04-15 | 2009-07-30 | Shizuko Sei | North-2'deoxy -methanocarbathymidines as antiviral agents for treatment of kaposi's sarcoma-associated herpes virus |
| US7867983B2 (en) * | 2007-03-29 | 2011-01-11 | The University Of Connecticut | Methods to protect skeletal muscle against injury |
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2005
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- 2005-09-02 CN CN2005800363201A patent/CN101056879B/zh not_active Expired - Fee Related
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2007
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2012
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2005285284A1 (en) | 2006-03-23 |
| BRPI0515030A (pt) | 2008-07-01 |
| JP2012229215A (ja) | 2012-11-22 |
| IL181716A0 (en) | 2007-07-04 |
| CN101056879B (zh) | 2011-10-05 |
| JP2008512457A (ja) | 2008-04-24 |
| CN101056879A (zh) | 2007-10-17 |
| KR20070050484A (ko) | 2007-05-15 |
| AU2005285284B2 (en) | 2011-06-02 |
| WO2006031505A1 (en) | 2006-03-23 |
| US20070232626A1 (en) | 2007-10-04 |
| EP1794162A1 (en) | 2007-06-13 |
| US7825126B2 (en) | 2010-11-02 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130829 |