RU2007109794A - Модуляторы мускариновых рецепторов - Google Patents
Модуляторы мускариновых рецепторов Download PDFInfo
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- RU2007109794A RU2007109794A RU2007109794/04A RU2007109794A RU2007109794A RU 2007109794 A RU2007109794 A RU 2007109794A RU 2007109794/04 A RU2007109794/04 A RU 2007109794/04A RU 2007109794 A RU2007109794 A RU 2007109794A RU 2007109794 A RU2007109794 A RU 2007109794A
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- aliphatic
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- 125000001931 aliphatic group Chemical group 0.000 claims 42
- 150000001875 compounds Chemical class 0.000 claims 39
- 125000001424 substituent group Chemical group 0.000 claims 31
- -1 alkoxyalkoxycarbonyl Chemical group 0.000 claims 17
- 229910052736 halogen Inorganic materials 0.000 claims 14
- 150000002367 halogens Chemical class 0.000 claims 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 8
- 125000003118 aryl group Chemical group 0.000 claims 8
- 125000002619 bicyclic group Chemical group 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 125000004429 atom Chemical group 0.000 claims 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 125000000623 heterocyclic group Chemical group 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 229930004006 tropane Natural products 0.000 claims 5
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 4
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims 4
- 125000006168 tricyclic group Chemical group 0.000 claims 4
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims 3
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 208000002193 Pain Diseases 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 2
- 125000005225 alkynyloxycarbonyl group Chemical group 0.000 claims 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 2
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000004475 heteroaralkyl group Chemical group 0.000 claims 2
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- 150000003813 tropane derivatives Chemical class 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 1
- 208000020925 Bipolar disease Diseases 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 208000024412 Friedreich ataxia Diseases 0.000 claims 1
- 208000010412 Glaucoma Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 206010026749 Mania Diseases 0.000 claims 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims 1
- 102000007207 Muscarinic M1 Receptor Human genes 0.000 claims 1
- 108010008406 Muscarinic M1 Receptor Proteins 0.000 claims 1
- 102000007216 Muscarinic M4 Receptor Human genes 0.000 claims 1
- 108010008414 Muscarinic M4 Receptor Proteins 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000028017 Psychotic disease Diseases 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 208000016620 Tourette disease Diseases 0.000 claims 1
- 201000004810 Vascular dementia Diseases 0.000 claims 1
- 208000005946 Xerostomia Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 208000006218 bradycardia Diseases 0.000 claims 1
- 230000036471 bradycardia Effects 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 208000022371 chronic pain syndrome Diseases 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010013781 dry mouth Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 210000004051 gastric juice Anatomy 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 208000028774 intestinal disease Diseases 0.000 claims 1
- 230000004410 intraocular pressure Effects 0.000 claims 1
- 206010023332 keratitis Diseases 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 230000007170 pathology Effects 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 230000028327 secretion Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
- 0 C*c1c[o]cc1 Chemical compound C*c1c[o]cc1 0.000 description 4
- YYDNBUBMBZRNQQ-UHFFFAOYSA-N Cc(cc1)ccc1S(C)(=O)=O Chemical compound Cc(cc1)ccc1S(C)(=O)=O YYDNBUBMBZRNQQ-UHFFFAOYSA-N 0.000 description 1
- LRLRAYMYEXQKID-UHFFFAOYSA-N Cc1ccc(C(F)(F)F)cc1 Chemical compound Cc1ccc(C(F)(F)F)cc1 LRLRAYMYEXQKID-UHFFFAOYSA-N 0.000 description 1
- VSGXHZUTTFLSBC-UHFFFAOYSA-N Sc1c[s]cc1 Chemical compound Sc1c[s]cc1 VSGXHZUTTFLSBC-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4747—Quinolines; Isoquinolines spiro-condensed
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- C—CHEMISTRY; METALLURGY
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- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
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- C07D223/32—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems containing carbocyclic rings other than six-membered
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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Applications Claiming Priority (2)
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| US60273104P | 2004-08-19 | 2004-08-19 | |
| US60/602,731 | 2004-08-19 |
Publications (1)
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| RU2007109794A true RU2007109794A (ru) | 2008-09-27 |
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| RU2007109794/04A RU2007109794A (ru) | 2004-08-19 | 2005-08-19 | Модуляторы мускариновых рецепторов |
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| JP (3) | JP2008510728A (enExample) |
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| CN (1) | CN101031296A (enExample) |
| AU (1) | AU2005277126A1 (enExample) |
| CA (1) | CA2577677A1 (enExample) |
| IL (1) | IL181388A0 (enExample) |
| MX (1) | MX2007002033A (enExample) |
| NO (1) | NO20071272L (enExample) |
| NZ (1) | NZ553202A (enExample) |
| RU (1) | RU2007109794A (enExample) |
| TW (1) | TW200621244A (enExample) |
| WO (1) | WO2006023852A2 (enExample) |
| ZA (1) | ZA200701397B (enExample) |
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| JP4712384B2 (ja) * | 2002-09-09 | 2011-06-29 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Orl−1受容体介在障害の治療に有用なヒドロキシアルキル置換1,3,8−トリアザスピロ[4.5]デカン−4−オン誘導体 |
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| WO2006130416A2 (en) * | 2005-06-02 | 2006-12-07 | Janssen Pharmaceutica, N.V. | Novel 3-spirocyclic indolyl derivatives useful as orl-1 receptor modulators |
| JP2009507800A (ja) | 2005-09-09 | 2009-02-26 | ユーロ−セルティーク エス.エイ. | 縮合およびスピロ環化合物ならびにその使用 |
| WO2007076070A2 (en) * | 2005-12-22 | 2007-07-05 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
| WO2007100670A1 (en) * | 2006-02-22 | 2007-09-07 | Vertex Pharmaceuticals Incorporated | Spiro condensed piperidnes as modulators of muscarinic receptors |
| KR20080094964A (ko) * | 2006-02-22 | 2008-10-27 | 버텍스 파마슈티칼스 인코포레이티드 | 무스카린성 수용체의 조절제 |
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| CN101500565A (zh) * | 2006-06-29 | 2009-08-05 | 弗特克斯药品有限公司 | 毒蕈碱性受体的调节剂 |
| CA2660974A1 (en) * | 2006-08-18 | 2008-02-21 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
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| CN102464663B (zh) * | 2010-11-11 | 2015-05-27 | 上海合全药物研发有限公司 | 1’-叔丁氧羰基-螺[苯并二氢吡喃-4,4’-哌啶]-2-甲酸的合成方法 |
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| TW201711999A (zh) | 2015-09-03 | 2017-04-01 | 佛瑪治療公司 | ﹝6,6﹞稠合雙環組蛋白脫乙醯基酶8(hdac8)抑制劑 |
| CN108264535A (zh) | 2016-12-30 | 2018-07-10 | 中国科学院上海药物研究所 | 一种抗抑郁化合物及其制备方法和应用 |
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2005
- 2005-08-19 EP EP05792897A patent/EP1781288A2/en not_active Withdrawn
- 2005-08-19 RU RU2007109794/04A patent/RU2007109794A/ru not_active Application Discontinuation
- 2005-08-19 JP JP2007528089A patent/JP2008510728A/ja active Pending
- 2005-08-19 CA CA002577677A patent/CA2577677A1/en not_active Abandoned
- 2005-08-19 WO PCT/US2005/029780 patent/WO2006023852A2/en not_active Ceased
- 2005-08-19 NZ NZ553202A patent/NZ553202A/en not_active IP Right Cessation
- 2005-08-19 AU AU2005277126A patent/AU2005277126A1/en not_active Abandoned
- 2005-08-19 US US11/208,386 patent/US7879834B2/en active Active
- 2005-08-19 KR KR1020077006166A patent/KR20070046929A/ko not_active Withdrawn
- 2005-08-19 EP EP11155136A patent/EP2364705A3/en not_active Withdrawn
- 2005-08-19 CN CNA2005800325784A patent/CN101031296A/zh active Pending
- 2005-08-19 EP EP11155135A patent/EP2374455A3/en not_active Withdrawn
- 2005-08-19 TW TW094128467A patent/TW200621244A/zh unknown
- 2005-08-19 MX MX2007002033A patent/MX2007002033A/es not_active Application Discontinuation
-
2007
- 2007-02-15 IL IL181388A patent/IL181388A0/en unknown
- 2007-02-16 ZA ZA200701397A patent/ZA200701397B/xx unknown
- 2007-03-08 NO NO20071272A patent/NO20071272L/no not_active Application Discontinuation
-
2010
- 2010-05-24 US US12/785,676 patent/US8258148B2/en not_active Expired - Fee Related
-
2012
- 2012-02-24 JP JP2012039210A patent/JP2012107055A/ja not_active Withdrawn
- 2012-02-24 JP JP2012039208A patent/JP2012107054A/ja not_active Withdrawn
- 2012-07-11 US US13/546,185 patent/US8497295B2/en not_active Expired - Fee Related
-
2013
- 2013-06-17 US US13/919,369 patent/US20130281476A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NZ553202A (en) | 2010-12-24 |
| AU2005277126A1 (en) | 2006-03-02 |
| CN101031296A (zh) | 2007-09-05 |
| US8497295B2 (en) | 2013-07-30 |
| CA2577677A1 (en) | 2006-03-02 |
| KR20070046929A (ko) | 2007-05-03 |
| TW200621244A (en) | 2006-07-01 |
| NO20071272L (no) | 2007-04-17 |
| JP2012107055A (ja) | 2012-06-07 |
| US20120283243A1 (en) | 2012-11-08 |
| US20100311720A1 (en) | 2010-12-09 |
| EP2374455A2 (en) | 2011-10-12 |
| EP2374455A3 (en) | 2012-03-28 |
| US20060079505A1 (en) | 2006-04-13 |
| IL181388A0 (en) | 2007-07-04 |
| MX2007002033A (es) | 2007-04-26 |
| US20130281476A1 (en) | 2013-10-24 |
| EP1781288A2 (en) | 2007-05-09 |
| WO2006023852A2 (en) | 2006-03-02 |
| JP2012107054A (ja) | 2012-06-07 |
| US7879834B2 (en) | 2011-02-01 |
| JP2008510728A (ja) | 2008-04-10 |
| WO2006023852A3 (en) | 2006-08-31 |
| ZA200701397B (en) | 2009-04-29 |
| EP2364705A2 (en) | 2011-09-14 |
| EP2364705A3 (en) | 2012-04-04 |
| US8258148B2 (en) | 2012-09-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA94 | Acknowledgement of application withdrawn (non-payment of fees) |
Effective date: 20101013 |