CA2634644A1 - 8-pyrazinyl-5-spiropyrimidinetrione-oxazinoquinoline derivatives as antibacterial agents - Google Patents
8-pyrazinyl-5-spiropyrimidinetrione-oxazinoquinoline derivatives as antibacterial agents Download PDFInfo
- Publication number
- CA2634644A1 CA2634644A1 CA002634644A CA2634644A CA2634644A1 CA 2634644 A1 CA2634644 A1 CA 2634644A1 CA 002634644 A CA002634644 A CA 002634644A CA 2634644 A CA2634644 A CA 2634644A CA 2634644 A1 CA2634644 A1 CA 2634644A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- substituted
- dimethyl
- oxazino
- spiro
- 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
- 239000003242 anti bacterial agent Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 238000000034 method Methods 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 8
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 8
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 8
- -1 -OR6 Chemical group 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 150000002367 halogens Chemical class 0.000 claims description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 25
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 25
- 150000002170 ethers Chemical class 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000003003 spiro group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 241000894006 Bacteria Species 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims description 8
- 108090000765 processed proteins & peptides Chemical group 0.000 claims description 8
- 150000003216 pyrazines Chemical class 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 150000007529 inorganic bases Chemical class 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical group OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000010537 deprotonation reaction Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 239000007818 Grignard reagent Substances 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 150000004795 grignard reagents Chemical class 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
- SSQYBZNZBNXQNO-LIBAHTEVSA-N (2'r,4's,4'as)-9',10'-difluoro-2',4'-dimethyl-8'-(5-methylpyrazin-2-yl)spiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C12([C@@H]3N(C4=C(F)C(F)=C(C=C4C1)C=1N=CC(C)=NC=1)C[C@H](O[C@H]3C)C)C(=O)NC(=O)NC2=O SSQYBZNZBNXQNO-LIBAHTEVSA-N 0.000 claims 3
- WJWQTPKPCGYBAH-KSRUKNBBSA-N (2'r,4's,4'as)-8'-(5-aminopyrazin-2-yl)-9',10'-difluoro-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C12([C@@H]3N(C4=C(F)C(F)=C(C=C4C1)C=1N=CC(N)=NC=1)C[C@H](O[C@H]3C)C)C(=O)NC(=O)NC2=O WJWQTPKPCGYBAH-KSRUKNBBSA-N 0.000 claims 1
- XHSMJCDFOZQTSG-KSRUKNBBSA-N (2'r,4's,4'as)-8'-(5-bromopyrazin-2-yl)-9',10'-difluoro-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C12([C@@H]3N(C4=C(F)C(F)=C(C=C4C1)C=1N=CC(Br)=NC=1)C[C@H](O[C@H]3C)C)C(=O)NC(=O)NC2=O XHSMJCDFOZQTSG-KSRUKNBBSA-N 0.000 claims 1
- AESOLELBNNKZEG-RMDKCXRXSA-N (2'r,4's,4'as)-8'-(5-ethoxypyrazin-2-yl)-9',10'-difluoro-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C1=NC(OCC)=CN=C1C(C(=C1F)F)=CC2=C1N1C[C@@H](C)O[C@@H](C)[C@@H]1C1(C(NC(=O)NC1=O)=O)C2 AESOLELBNNKZEG-RMDKCXRXSA-N 0.000 claims 1
- XASLRGGSKMMAAO-IOKPGSKQSA-N (2'r,4's,4'as)-9',10'-difluoro-2',4'-dimethyl-1,3-bis(morpholin-4-ylmethyl)-8'-pyrazin-2-ylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound O=C1N(CN2CCOCC2)C(=O)N(CN2CCOCC2)C(=O)C1([C@@H]1N(C2=C(F)C=3F)C[C@H](O[C@H]1C)C)CC2=CC=3C1=CN=CC=N1 XASLRGGSKMMAAO-IOKPGSKQSA-N 0.000 claims 1
- NKEIYQIDLBODBA-UETOGOEVSA-N (2'r,4's,4'as)-9',10'-difluoro-2',4'-dimethyl-1,3-bis[(4-methylpiperazin-1-yl)methyl]-8'-pyrazin-2-ylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound O=C1N(CN2CCN(C)CC2)C(=O)N(CN2CCN(C)CC2)C(=O)C1([C@@H]1N(C2=C(F)C=3F)C[C@H](O[C@H]1C)C)CC2=CC=3C1=CN=CC=N1 NKEIYQIDLBODBA-UETOGOEVSA-N 0.000 claims 1
- PBNUIWUNGLZCCQ-AUSHCKSDSA-N (2'r,4's,4'as)-9',10'-difluoro-8'-(5-methoxypyrazin-2-yl)-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C1=NC(OC)=CN=C1C(C(=C1F)F)=CC2=C1N1C[C@@H](C)O[C@@H](C)[C@@H]1C1(C(NC(=O)NC1=O)=O)C2 PBNUIWUNGLZCCQ-AUSHCKSDSA-N 0.000 claims 1
- HRTLIFOGJJTTBX-CRTZDJKQSA-N (2's,4'r,4'ar)-1,3-bis(bromomethyl)-9',10'-difluoro-2',4'-dimethyl-8'-pyrazin-2-ylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C12([C@H]3N(C4=C(F)C(F)=C(C=C4C1)C=1N=CC=NC=1)C[C@@H](O[C@@H]3C)C)C(=O)N(CBr)C(=O)N(CBr)C2=O HRTLIFOGJJTTBX-CRTZDJKQSA-N 0.000 claims 1
- AVCOPTRSDFHZJE-CRTZDJKQSA-N (2's,4'r,4'ar)-9',10'-difluoro-1,3-bis(hydroxymethyl)-2',4'-dimethyl-8'-pyrazin-2-ylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1h-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione Chemical compound C12([C@H]3N(C4=C(F)C(F)=C(C=C4C1)C=1N=CC=NC=1)C[C@@H](O[C@@H]3C)C)C(=O)N(CO)C(=O)N(CO)C2=O AVCOPTRSDFHZJE-CRTZDJKQSA-N 0.000 claims 1
- 229910018828 PO3H2 Inorganic materials 0.000 claims 1
- 230000003385 bacteriostatic effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 178
- 238000006243 chemical reaction Methods 0.000 description 90
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 45
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- 235000019341 magnesium sulphate Nutrition 0.000 description 25
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- 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
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75326205P | 2005-12-22 | 2005-12-22 | |
| US60/753,262 | 2005-12-22 | ||
| PCT/IB2006/003641 WO2007072151A1 (en) | 2005-12-22 | 2006-12-11 | 8-pyrazinyl-s-spiropyrimidinetrione-oxazinoquinoline derivatives as antibacterial agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2634644A1 true CA2634644A1 (en) | 2007-06-28 |
Family
ID=37872452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002634644A Abandoned CA2634644A1 (en) | 2005-12-22 | 2006-12-11 | 8-pyrazinyl-5-spiropyrimidinetrione-oxazinoquinoline derivatives as antibacterial agents |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7557100B2 (https=) |
| EP (2) | EP1971612A1 (https=) |
| JP (1) | JP5513743B2 (https=) |
| AR (1) | AR058701A1 (https=) |
| CA (1) | CA2634644A1 (https=) |
| DO (1) | DOP2006000268A (https=) |
| GT (1) | GT200600520A (https=) |
| NL (1) | NL2000373C2 (https=) |
| PE (1) | PE20071137A1 (https=) |
| TW (1) | TW200734344A (https=) |
| UY (1) | UY30030A1 (https=) |
| WO (1) | WO2007072151A1 (https=) |
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|---|---|---|---|---|
| ES2552682T3 (es) | 2003-03-10 | 2015-12-01 | Merck Sharp & Dohme Corp. | Agentes antibacterianos novedosos |
| DOP2006000268A (es) * | 2005-12-22 | 2007-07-31 | Pfizer Prod Inc | Agentes antibacterianos |
| US20100261719A1 (en) * | 2007-07-02 | 2010-10-14 | Gregory Steven Basarab | Chemical compounds |
| CA2729923A1 (en) * | 2007-07-06 | 2009-01-15 | Aarhus Universitet | Dehydrated chitosan nanoparticles |
| CN101687871A (zh) | 2007-07-16 | 2010-03-31 | 阿斯利康(瑞典)有限公司 | 用作抗菌剂的螺缩合巴比妥酸衍生物 |
| CN105732745A (zh) | 2007-10-25 | 2016-07-06 | 森普拉制药公司 | 大环内酯类抗菌剂的制备方法 |
| US9040528B2 (en) | 2008-10-14 | 2015-05-26 | Astrazeneca Ab | Chemical compounds 542 |
| CN102245605B (zh) * | 2008-10-14 | 2016-01-27 | 阿斯利康(瑞典)有限公司 | 用于治疗细菌感染的稠合、螺环杂芳族化合物 |
| AU2009308182B2 (en) * | 2008-10-24 | 2016-05-19 | Cempra Pharmaceuticals, Inc. | Biodefenses using triazole-containing macrolides |
| US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
| US9480679B2 (en) | 2009-09-10 | 2016-11-01 | Cempra Pharmaceuticals, Inc. | Methods for treating malaria, tuberculosis and MAC diseases |
| DK2550286T3 (en) | 2010-03-22 | 2016-02-29 | Cempra Pharmaceuticals Inc | CRYSTALLINE FORMS OF A MACROLID AND APPLICATIONS THEREOF |
| CN105198944B (zh) | 2010-05-20 | 2018-06-01 | 森普拉制药公司 | 制备大环内酯和酮内酯及其中间体的方法 |
| EP2613630A4 (en) | 2010-09-10 | 2014-01-15 | Cempra Pharmaceuticals Inc | HYDROGEN BOND FOR THE PREPARATION OF FLUOROCHETOLIDES FOR THE TREATMENT OF DISEASES |
| MX2014011537A (es) | 2012-03-27 | 2015-02-10 | Cempra Pharmaceuticals Inc | Formulaciones parenterales para la administracion de antibioticos macrolidos. |
| US8952149B2 (en) | 2012-09-26 | 2015-02-10 | Zoetis Llc | Tricyclic tetrahydroquinoline antibacterial agents |
| US8889671B2 (en) | 2013-01-23 | 2014-11-18 | Astrazeneca Ab | Compounds and methods for treating bacterial infections |
| HK1217665A1 (zh) | 2013-03-14 | 2017-01-20 | 森普拉制药公司 | 用於治療呼吸道疾病的方法及其製劑 |
| RU2015138797A (ru) | 2013-03-15 | 2017-04-24 | Семпра Фармасьютикалс, Инк. | Конвергентные способы получения макролидных антибактериальных агентов |
| SG10201906842WA (en) | 2014-05-29 | 2019-08-27 | Entasis Therapeutics Ltd | Fused, spirocyclic heteroaromatic compounds for the treatment of bacterial infections |
| UY36851A (es) | 2015-08-16 | 2017-03-31 | Glaxosmithkline Ip Dev Ltd | Compuestos para uso en aplicaciones antibacterianas |
| KR102717819B1 (ko) | 2017-07-28 | 2024-10-14 | 다케다 야쿠힌 고교 가부시키가이샤 | Tyk2 억제제 및 이의 용도 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5011860A (en) | 1986-04-11 | 1991-04-30 | Schering Corporation | Aryl-substituted naphthyridine and pyridopyrazine derivatives and their use in treating hyperproliferative skin diseases |
| DE19502178A1 (de) | 1994-01-27 | 1995-08-03 | Hoechst Ag | Thiadiazolderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Vorprodukte zur Herstellung von Flüssigkristallen |
| US6608081B2 (en) * | 1999-08-12 | 2003-08-19 | Ortho-Mcneil Pharmaceutical, Inc. | Bicyclic heterocyclic substituted phenyl oxazolidinone antibacterials, and related compositions and methods |
| CN1501937A (zh) | 2000-10-26 | 2004-06-02 | �Ʒ� | 螺-嘧啶-2,4,6-三酮金属蛋白酶抑制剂 |
| ATE315038T1 (de) * | 2001-05-30 | 2006-02-15 | Warner Lambert Co | Antibakterielle mittel |
| AU2003228701A1 (en) | 2002-04-25 | 2003-11-10 | Bristol-Myers Squibb Company | Spirobarbituric acid derivatives useful as inhibitors of matrix metalloproteases |
| US7208490B2 (en) | 2002-10-07 | 2007-04-24 | Pharmacia & Upjohn Company Llc | Tricyclic tetrahydroquinoline antibacterial agents |
| CA2606847A1 (en) | 2005-05-09 | 2006-11-16 | Warner-Lambert Company Llc | Antibacterial agents |
| DOP2006000268A (es) * | 2005-12-22 | 2007-07-31 | Pfizer Prod Inc | Agentes antibacterianos |
-
2006
- 2006-11-29 DO DO2006000268A patent/DOP2006000268A/es unknown
- 2006-12-11 WO PCT/IB2006/003641 patent/WO2007072151A1/en not_active Ceased
- 2006-12-11 CA CA002634644A patent/CA2634644A1/en not_active Abandoned
- 2006-12-11 EP EP06831728A patent/EP1971612A1/en not_active Withdrawn
- 2006-12-11 JP JP2008546665A patent/JP5513743B2/ja not_active Expired - Fee Related
- 2006-12-11 EP EP13151044.8A patent/EP2620439A1/en not_active Withdrawn
- 2006-12-13 NL NL2000373A patent/NL2000373C2/nl not_active IP Right Cessation
- 2006-12-19 UY UY30030A patent/UY30030A1/es not_active Application Discontinuation
- 2006-12-19 US US11/641,215 patent/US7557100B2/en not_active Expired - Fee Related
- 2006-12-20 AR ARP060105669A patent/AR058701A1/es unknown
- 2006-12-20 PE PE2006001657A patent/PE20071137A1/es not_active Application Discontinuation
- 2006-12-20 GT GT200600520A patent/GT200600520A/es unknown
- 2006-12-21 TW TW095148255A patent/TW200734344A/zh unknown
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2009
- 2009-07-15 US US12/503,123 patent/US20090275536A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| UY30030A1 (es) | 2007-07-31 |
| NL2000373A1 (nl) | 2007-06-26 |
| US20090275536A1 (en) | 2009-11-05 |
| US7557100B2 (en) | 2009-07-07 |
| AR058701A1 (es) | 2008-02-20 |
| GT200600520A (es) | 2007-07-17 |
| TW200734344A (en) | 2007-09-16 |
| NL2000373C2 (nl) | 2010-02-02 |
| US20070197518A1 (en) | 2007-08-23 |
| DOP2006000268A (es) | 2007-07-31 |
| WO2007072151A1 (en) | 2007-06-28 |
| JP5513743B2 (ja) | 2014-06-04 |
| PE20071137A1 (es) | 2008-01-10 |
| JP2009520804A (ja) | 2009-05-28 |
| EP1971612A1 (en) | 2008-09-24 |
| EP2620439A1 (en) | 2013-07-31 |
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