CO5320600A1 - Agentes antibacterianos de 3-aminoquinazolin-2,4-dionas - Google Patents
Agentes antibacterianos de 3-aminoquinazolin-2,4-dionasInfo
- Publication number
- CO5320600A1 CO5320600A1 CO01004183A CO01004183A CO5320600A1 CO 5320600 A1 CO5320600 A1 CO 5320600A1 CO 01004183 A CO01004183 A CO 01004183A CO 01004183 A CO01004183 A CO 01004183A CO 5320600 A1 CO5320600 A1 CO 5320600A1
- Authority
- CO
- Colombia
- Prior art keywords
- substituted
- alkyl
- alkynyl
- alkenyl
- heterocyclic
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/04—Ortho-condensed systems
-
- 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
-
- 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
- C07D487/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Paper (AREA)
Abstract
Un compuespo de la fórmula I<EMI FILE="01004183_1" ID="1" IMF=JPEG >o una sal farmacéuticamente aceptable de ellos en donde:R1 y R3 independientemente son H,Alquilo y alquilo sustituido de C1-C12,AIquenilo y alquenilo sustituido de C2-C12,AlquiniIo y alquinilo sustituido de C2-C12,Cicloalquilo y cicloalquiIo sustituido de C3-C12,Arilo y arilo sustituido,Heterocíclico y heterocíclico sustituido,o heteroarilo y heteroarilo sustituido;R5, R6 y R8 independientemente son H,(O)nalquilo de C1-C12, y alquilo sustituido;(O)nalquenilo de C2-C12 y alquenilo sustituido;(O)nalquinilo de C2-C12 y alquinilo sustituido,en donde n es 0 o 1,halo,NO2,CN,NR´R´´;R´ y R´´ independientemente son H,alquilo y alquilo sustituido de C1-C12,alquenilo y alquenilo sustituido de C2-C12,alquinilo y alquinilo sustituido de C2-C12,CO-alquilo de C1-C12 y alquilo sustituido,o R´ y R´´ tomados junto con el nitrógeno al cual están unidos forman un anillo de 3 a 7 miembros que contiene de 1 a 3 heteroátomos seleccionados de N, O y S, dicho anillo es no sustituido o sustituido con hasta 4 grupos sustituyentes;R1 y R8 pueden ser tomados junto con los átomos a los cuales están unidos para formar un anillo cíclico que tiene de 1 a 3 heteroátomos seleccionados de N, O y S y optativamente sustituidos por R´ y R´´; - 2 -R7 es hidrógeno,alquilo y alquilo sustituido de C1-C12,alquenilo y alquenilo sustituido de C2-C12,alquinilo y alquinilo sustituido de C2-C12,halo,NO2,CN,NR´R´´,COOR´ ,arilo,arilo fusionado,heterocíclico,heterocíclico bicíclico, oespiro heterocíclicoen donde todos los grupos del anillo pueden ser sustituidos; yJ y K independientemente son C o N, siempre que cuando J o K es N, R6 o R8 esté ausente en esa posición.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17825200P | 2000-01-24 | 2000-01-24 | |
US24126700P | 2000-10-18 | 2000-10-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
CO5320600A1 true CO5320600A1 (es) | 2003-09-30 |
Family
ID=26874138
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CO01004183A CO5320600A1 (es) | 2000-01-24 | 2001-01-22 | Agentes antibacterianos de 3-aminoquinazolin-2,4-dionas |
Country Status (38)
Country | Link |
---|---|
US (2) | US7094780B1 (es) |
EP (1) | EP1255739B1 (es) |
JP (1) | JP4811978B2 (es) |
KR (1) | KR20020067701A (es) |
CN (1) | CN1425008A (es) |
AP (1) | AP2002002603A0 (es) |
AR (1) | AR030186A1 (es) |
AT (1) | ATE398110T1 (es) |
AU (1) | AU783078B2 (es) |
BG (1) | BG107023A (es) |
BR (1) | BR0017010A (es) |
CA (1) | CA2393802C (es) |
CO (1) | CO5320600A1 (es) |
CR (1) | CR6709A (es) |
DE (1) | DE60039194D1 (es) |
EA (1) | EA005585B1 (es) |
EE (1) | EE200200412A (es) |
ES (1) | ES2304992T3 (es) |
GE (1) | GEP20053429B (es) |
HK (1) | HK1054237A1 (es) |
HN (1) | HN2001000009A (es) |
HR (1) | HRP20020696A2 (es) |
HU (1) | HUP0204101A3 (es) |
IL (1) | IL150393A0 (es) |
IS (1) | IS6448A (es) |
MA (1) | MA26866A1 (es) |
MX (1) | MXPA02005989A (es) |
NO (1) | NO20023516D0 (es) |
OA (1) | OA12316A (es) |
PA (1) | PA8510101A1 (es) |
PE (1) | PE20011060A1 (es) |
PL (1) | PL356837A1 (es) |
SK (1) | SK10572002A3 (es) |
SV (1) | SV2001000288A (es) |
TN (1) | TNSN01011A1 (es) |
UY (1) | UY26551A1 (es) |
WO (1) | WO2001053273A1 (es) |
YU (1) | YU55902A (es) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69840599D1 (de) | 1997-09-15 | 2009-04-09 | Procter & Gamble | Antimikrobielle chinolone, ihre zusammensetzungen und ihre verwendungen |
JP2004532876A (ja) | 2001-05-30 | 2004-10-28 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 抗菌剤 |
WO2002102793A2 (en) * | 2001-06-19 | 2002-12-27 | Warner-Lambert Company Llc | Quinazolinediones as antibacterial agents |
US6900224B2 (en) * | 2002-07-31 | 2005-05-31 | The Procter & Gamble Company | Antimicrobial quinolones, their compositions and uses |
JP2007505096A (ja) * | 2003-09-12 | 2007-03-08 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | キノロン抗菌剤 |
WO2005026153A1 (en) * | 2003-09-12 | 2005-03-24 | Warner-Lambert Company Llc | Quinazoline-2, 4-diones as antibacterial agents |
JP2007511597A (ja) * | 2003-11-18 | 2007-05-10 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | 抗菌アミノキナゾリヂンヂオン誘導体 |
WO2006019965A2 (en) * | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
GB0416730D0 (en) | 2004-07-27 | 2004-09-01 | Novartis Ag | Organic compounds |
ATE447572T1 (de) * | 2005-01-26 | 2009-11-15 | Hoffmann La Roche | Phenylmethanonderivate und ihre verwendung als glycin-transporter-1-hemmer |
GB0507298D0 (en) | 2005-04-11 | 2005-05-18 | Novartis Ag | Organic compounds |
US7977346B2 (en) | 2006-01-17 | 2011-07-12 | Guoqing Paul Chen | Spiro compounds and methods of use |
PT2001862E (pt) | 2006-03-28 | 2011-07-20 | Warner Chilcott Co Llc | Sais de malato e polimorfos do ácido (3s,5s)-7-[3- amino-5-metil-piperidinil]-1-ciclopropil-1,4-dihidro- 8-metoxi-4-oxo-3-quinolinocarboxílico |
CA2647454A1 (en) | 2006-03-28 | 2007-10-04 | The Procter & Gamble Company | A coupling process for preparing quinolone intermediates |
US20080139574A1 (en) | 2006-11-30 | 2008-06-12 | Cadila Healthcare Limited | Novel quinoline derivatives |
AU2009209811B2 (en) * | 2008-01-30 | 2011-07-21 | Shin Poong Pharmaceutical Co., Ltd. | Novel quinazoline-2,4-dione derivative, and medical compositions for the prophylaxis and treatment of cranial nerve disease containing the same |
WO2011031745A1 (en) | 2009-09-09 | 2011-03-17 | Achaogen, Inc. | Antibacterial fluoroquinolone analogs |
WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
AR085806A1 (es) | 2011-03-15 | 2013-10-30 | Trius Therapeutics Inc | Inhibidores triciclicos de girasa |
RU2618673C2 (ru) * | 2011-12-21 | 2017-05-10 | Цзянсу Хэнжуй Медсин Ко., Лтд. | Производные пирролопиримидина, полезные в качестве ингибиторов jak-киназы |
SI3495367T1 (sl) | 2012-06-13 | 2021-01-29 | Incyte Holdings Corporation | Substituirane triciklične spojine kot zaviralci FGFR |
US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
CN105189505B (zh) | 2012-09-12 | 2019-03-22 | 默克夏普&多梅有限公司 | 用作抗菌剂的三环促旋酶抑制剂 |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
JP6449244B2 (ja) | 2013-04-19 | 2019-01-09 | インサイト・ホールディングス・コーポレイションIncyte Holdings Corporation | Fgfr抑制剤としての二環式複素環 |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
CN108530448A (zh) * | 2017-03-02 | 2018-09-14 | 浙江司太立制药股份有限公司 | 含有碱性氮杂螺环片段的苯并噻嗪-4-酮类化合物及其制备方法 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
US11466004B2 (en) | 2018-05-04 | 2022-10-11 | Incyte Corporation | Solid forms of an FGFR inhibitor and processes for preparing the same |
EA202092649A1 (ru) | 2018-05-04 | 2021-06-21 | Инсайт Корпорейшн | Соли ингибитора fgfr |
CN111620866A (zh) * | 2019-02-27 | 2020-09-04 | 南京药石科技股份有限公司 | 一种顺式-7,7-二氟-六氢-1H 吡咯并[3,4-c]吡啶衍生物及其制备方法 |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
AU2020366006A1 (en) | 2019-10-14 | 2022-04-21 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
CN115151539A (zh) | 2019-12-04 | 2022-10-04 | 因赛特公司 | Fgfr抑制剂的衍生物 |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN111499513B (zh) * | 2020-04-24 | 2023-03-14 | 上海毕得医药科技股份有限公司 | 一种2,3,4,5-四溴苯甲酸酯的合成方法 |
CA3215903A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
AR126102A1 (es) | 2021-06-09 | 2023-09-13 | Incyte Corp | Heterociclos tricíclicos como inhibidores de fgfr |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1068263B (es) * | 1959-11-05 | |||
FR1203542A (fr) * | 1958-02-25 | 1960-01-19 | Rhone Poulenc Sa | Nouveaux dérivés de la phénothiazine comportant en position 10 une chaîne pipérazinique et leurs procédés de préparation |
ATE8626T1 (de) * | 1980-03-10 | 1984-08-15 | Berri-Balzac Societe Dite: | 3-amino-(1h,3h)-2,4-chinazolindionderivate. |
GB2097784A (en) * | 1981-04-28 | 1982-11-10 | Davidson Dr John Stirton | Dihydrobenzotriazepine diones; aminoquinazoline diones |
WO1994014809A1 (de) | 1992-12-23 | 1994-07-07 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Anellierte uracilderivate |
WO1998018781A2 (en) | 1996-10-28 | 1998-05-07 | Versicor, Inc. | Fused 2,4-pyrimidinedione combinatorial libraries, their preparation and the use of fused 2,4-pyrimidinediones derivatives as antimicrobial agents |
SI1028950T1 (en) * | 1997-10-28 | 2003-08-31 | Warner-Lambert Company Llc | 7-substituted quinazolin-2,4-diones useful as antibacterial agents |
PL344248A1 (en) * | 1998-05-26 | 2001-10-22 | Warner Lambert Co | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
TR200101644T2 (tr) * | 1998-12-11 | 2001-11-21 | F.Hoffmann-La Roche Ag | TNF-ALFA önleyicileri olarak siklik hidrazin türevleri. |
-
2000
- 2000-12-12 US US10/182,221 patent/US7094780B1/en not_active Expired - Fee Related
- 2000-12-12 PL PL00356837A patent/PL356837A1/xx not_active Application Discontinuation
- 2000-12-12 EE EEP200200412A patent/EE200200412A/xx unknown
- 2000-12-12 CN CN00818578A patent/CN1425008A/zh active Pending
- 2000-12-12 MX MXPA02005989A patent/MXPA02005989A/es active IP Right Grant
- 2000-12-12 YU YU55902A patent/YU55902A/sh unknown
- 2000-12-12 CA CA2393802A patent/CA2393802C/en not_active Expired - Fee Related
- 2000-12-12 AT AT00984246T patent/ATE398110T1/de not_active IP Right Cessation
- 2000-12-12 EP EP00984246A patent/EP1255739B1/en not_active Expired - Lifetime
- 2000-12-12 BR BR0017010-0A patent/BR0017010A/pt not_active Application Discontinuation
- 2000-12-12 AU AU20899/01A patent/AU783078B2/en not_active Ceased
- 2000-12-12 KR KR1020027009515A patent/KR20020067701A/ko not_active Application Discontinuation
- 2000-12-12 DE DE60039194T patent/DE60039194D1/de not_active Expired - Lifetime
- 2000-12-12 HU HU0204101A patent/HUP0204101A3/hu unknown
- 2000-12-12 WO PCT/US2000/033656 patent/WO2001053273A1/en active Search and Examination
- 2000-12-12 AP APAP/P/2002/002603A patent/AP2002002603A0/en unknown
- 2000-12-12 OA OA1200200210A patent/OA12316A/en unknown
- 2000-12-12 EA EA200200661A patent/EA005585B1/ru not_active IP Right Cessation
- 2000-12-12 ES ES00984246T patent/ES2304992T3/es not_active Expired - Lifetime
- 2000-12-12 SK SK1057-2002A patent/SK10572002A3/sk unknown
- 2000-12-12 IL IL15039300A patent/IL150393A0/xx unknown
- 2000-12-12 GE GE4912A patent/GEP20053429B/en unknown
- 2000-12-12 JP JP2001553275A patent/JP4811978B2/ja not_active Expired - Fee Related
-
2001
- 2001-01-19 PA PA20018510101A patent/PA8510101A1/es unknown
- 2001-01-22 HN HN2001000009A patent/HN2001000009A/es unknown
- 2001-01-22 TN TNTNSN01011A patent/TNSN01011A1/en unknown
- 2001-01-22 UY UY26551A patent/UY26551A1/es not_active Application Discontinuation
- 2001-01-22 CO CO01004183A patent/CO5320600A1/es not_active Application Discontinuation
- 2001-01-22 SV SV2001000288A patent/SV2001000288A/es not_active Application Discontinuation
- 2001-01-22 PE PE2001000066A patent/PE20011060A1/es not_active Application Discontinuation
- 2001-01-23 AR ARP010100278A patent/AR030186A1/es unknown
-
2002
- 2002-06-27 IS IS6448A patent/IS6448A/is unknown
- 2002-07-19 CR CR6709A patent/CR6709A/es not_active Application Discontinuation
- 2002-07-22 MA MA26734A patent/MA26866A1/fr unknown
- 2002-07-23 NO NO20023516A patent/NO20023516D0/no not_active Application Discontinuation
- 2002-08-22 BG BG107023A patent/BG107023A/xx unknown
- 2002-08-23 HR HR20020696A patent/HRP20020696A2/hr not_active Application Discontinuation
-
2003
- 2003-09-11 HK HK03106519.6A patent/HK1054237A1/zh unknown
-
2006
- 2006-06-13 US US11/452,121 patent/US7582627B2/en not_active Expired - Fee Related
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