CO5251464A1 - Inhibidores de n-(5-(((5-alquil-2-oxazolil)metil)tio)-2- tiazolil)-carboxamida de cinasas dependientes de ciclina - Google Patents
Inhibidores de n-(5-(((5-alquil-2-oxazolil)metil)tio)-2- tiazolil)-carboxamida de cinasas dependientes de ciclinaInfo
- Publication number
- CO5251464A1 CO5251464A1 CO00095239A CO00095239A CO5251464A1 CO 5251464 A1 CO5251464 A1 CO 5251464A1 CO 00095239 A CO00095239 A CO 00095239A CO 00095239 A CO00095239 A CO 00095239A CO 5251464 A1 CO5251464 A1 CO 5251464A1
- Authority
- CO
- Colombia
- Prior art keywords
- alkyl
- oxazolil
- tiazolil
- uncle
- rent
- Prior art date
Links
- 108091000080 Phosphotransferase Proteins 0.000 title 1
- 230000001419 dependent effect Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 title 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 title 1
- 102000020233 phosphotransferase Human genes 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 5
- 239000001257 hydrogen Substances 0.000 abstract 4
- 229910052739 hydrogen Inorganic materials 0.000 abstract 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Abstract
Un compuesto de la formula I<EMI FILE="00095239_1" ID="1" IMF=JPEG >y enantiómeros, diasterómeros y sales farmacéuticamente aceptables del mismo, caracterizado porqueR es alquilo;R1 y R2 son cada uno independientemente hidrógeno o alquilo;R3 es hidrógeno o alquilo, y R4 es hidrógeno o alquilo sibstituido con uno o dos grupos hidroxi o un grupo NR5R6, o R3 y R4 se toman conjuntamente con el átomo de nitrógeno al cual están unidos para formar un anillo heterocíclico de 4 a 7 miembros, en donde R3R4 se representa por (CH2)n-, donde n es un número entero de 3, 4, 4 ó 6;R5 y R6 son cada uno independientemente hidrógeno, alquilo, alquilo substituido, cicloalquilo o cicloalquilo substituido, o R5 y R6 se toman conjuntamente con el átomo de nitrógeno al cual están unidos para formar un anillo heterocíclico de 4 a 7 miembros en donde R5R6 se representa por -(CH2)m-, donde m es un número entero de 3,4, 5 ó 6; yX es CH o N.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/464,511 US6262096B1 (en) | 1997-11-12 | 1999-12-15 | Aminothiazole inhibitors of cyclin dependent kinases |
US09/616,629 US6214852B1 (en) | 1998-10-21 | 2000-07-26 | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
Publications (1)
Publication Number | Publication Date |
---|---|
CO5251464A1 true CO5251464A1 (es) | 2003-02-28 |
Family
ID=27041009
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CO00095239A CO5251464A1 (es) | 1999-12-15 | 2000-12-14 | Inhibidores de n-(5-(((5-alquil-2-oxazolil)metil)tio)-2- tiazolil)-carboxamida de cinasas dependientes de ciclina |
Country Status (22)
Country | Link |
---|---|
US (1) | US6214852B1 (es) |
EP (1) | EP1240165B1 (es) |
JP (1) | JP2003525872A (es) |
KR (1) | KR20020067547A (es) |
CN (1) | CN1433415A (es) |
AT (1) | ATE294800T1 (es) |
AU (1) | AU774381B2 (es) |
CA (1) | CA2394544A1 (es) |
CO (1) | CO5251464A1 (es) |
CZ (1) | CZ20022013A3 (es) |
DE (1) | DE60019964T2 (es) |
DK (1) | DK1240165T3 (es) |
EE (1) | EE200200306A (es) |
ES (1) | ES2241678T3 (es) |
HU (1) | HUP0300974A3 (es) |
PE (1) | PE20010932A1 (es) |
PL (1) | PL364884A1 (es) |
PT (1) | PT1240165E (es) |
SI (1) | SI20975B (es) |
TW (1) | TWI265930B (es) |
UY (1) | UY26480A1 (es) |
WO (1) | WO2001044241A1 (es) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6262096B1 (en) | 1997-11-12 | 2001-07-17 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
US6414156B2 (en) * | 1998-10-21 | 2002-07-02 | Bristol-Myers Squibb Company | Process for preparing azacycloalkanoylaminothiazoles |
US6392053B2 (en) * | 1999-12-15 | 2002-05-21 | Bristol-Myers Squibb Company | Process for preparing arylacetylaminothiazoles |
US6515004B1 (en) | 1999-12-15 | 2003-02-04 | Bristol-Myers Squibb Company | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
US6534531B2 (en) * | 2000-04-27 | 2003-03-18 | Bristol-Myers Squibb Company | Methods for preventing and treating alopecia induced by chemotherapy or radiotherapy |
EA007392B1 (ru) * | 2001-07-19 | 2006-10-27 | Фармация Италия С.П.А. | Фенилацетамидотиазольные производные, способ их получения и их использования в качестве противоопухолевых средств |
EP1724270A3 (en) * | 2001-07-19 | 2007-01-03 | Pfizer Italia S.r.l. | Phenylacetamido-thiazole derivatives, process for their preparation and their use as antitumor agents |
ES2183734B1 (es) * | 2001-08-02 | 2004-06-16 | Consejo Sup. Investigaciones Cientificas | Derivados de 4-4'-bipiridil-2-2'-bisoxazoles y 4-4'-bipiridil-2-2'-bistiazoles como agentes antineoplasicos. |
BR0211626A (pt) * | 2001-08-03 | 2004-08-24 | Novo Nordisk As | Composto, uso do mesmo, composição farmacêutica, e, método para o tratamento de doenças, distúrbios, sìndromes e condições |
EP1417188A1 (en) * | 2001-08-03 | 2004-05-12 | Novo Nordisk A/S | Novel 2,4-diaminothiazole derivatives |
TW200401638A (en) * | 2002-06-20 | 2004-02-01 | Bristol Myers Squibb Co | Heterocyclic inhibitors of kinases |
DE10300124A1 (de) * | 2003-01-07 | 2004-07-15 | Bayer Ag | Verfahren zur Herstellung von Arylalkinen |
WO2005012875A2 (en) * | 2003-07-29 | 2005-02-10 | Bristol-Myers Squibb Company | Biomarkers of cyclin-dependent kinase modulation |
US7888504B2 (en) * | 2006-07-06 | 2011-02-15 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
US20080188524A1 (en) * | 2006-10-25 | 2008-08-07 | Martin Augustin | Methods of treating pain |
EP2519517B1 (en) | 2009-12-29 | 2015-03-25 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
LT2760860T (lt) * | 2011-09-28 | 2017-03-10 | Euro-Celtique S.A. | Azoto garstyčių dariniai |
EP2822935B1 (en) | 2011-11-17 | 2019-05-15 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-jun-n-terminal kinase (jnk) |
TWI573792B (zh) | 2012-02-01 | 2017-03-11 | 歐陸斯迪公司 | 新穎治療劑 |
EP2909194A1 (en) | 2012-10-18 | 2015-08-26 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2014063061A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
US20160264551A1 (en) | 2013-10-18 | 2016-09-15 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
EP3057956B1 (en) | 2013-10-18 | 2021-05-05 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
GB201409471D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409488D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409485D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
WO2016105528A2 (en) | 2014-12-23 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
US10550121B2 (en) | 2015-03-27 | 2020-02-04 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
WO2016201370A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
EP4019515A1 (en) * | 2015-09-09 | 2022-06-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
WO2018068832A1 (en) | 2016-10-11 | 2018-04-19 | Euro-Celtique S.A. | Hodgkin lymphoma therapy |
GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
GB201709403D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating sarcoma |
GB201709406D0 (en) | 2017-06-13 | 2017-07-26 | Euro-Cletique S A | Compounds for treating TNBC |
GB201709402D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating t-pll |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1088049A (en) | 1975-06-03 | 1980-10-21 | Takashi Masugi | 3-substituted-7-substituted alkanamido-3-cephem-4- carboxylic acid compounds and processes for preparation thereof |
CA1201431A (en) | 1981-12-17 | 1986-03-04 | Daiei Tunemoto | .beta.-LACTAM COMPOUNDS, PROCESS FOR THE PREPARATION THEREOF AND INTERMEDIATE PRODUCTS FOR THE PREPARATION THEREOF |
TW205041B (es) | 1989-08-07 | 1993-05-01 | Fujisawa Pharmaceutical Co | |
US5491157A (en) | 1993-05-10 | 1996-02-13 | Eastman Kodak Company | Method and composition for the prevention, control and amelioration of soilborne fungi and disease caused thereby |
IL112721A0 (en) | 1994-03-10 | 1995-05-26 | Zeneca Ltd | Azole derivatives |
JPH10510258A (ja) | 1994-12-09 | 1998-10-06 | 藤沢薬品工業株式会社 | セフェム化合物およびその医薬用途 |
IL117620A0 (en) | 1995-03-27 | 1996-07-23 | Fujisawa Pharmaceutical Co | Heterocyclic compounds processes for the preparation thereof and pharmaceutical compositions containing the same |
AUPN801196A0 (en) | 1996-02-12 | 1996-03-07 | Fujisawa Pharmaceutical Co., Ltd. | New cephem compounds and pharmaceutical use thereof |
YU22400A (sh) | 1997-10-27 | 2003-08-29 | Agouron Pharmaceuticals Inc. | Supstituisana 4-amino-tiazol-2-i jedinjenja kao cdks inhibitori |
US6040321A (en) | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
GB9823871D0 (en) | 1998-10-30 | 1998-12-23 | Pharmacia & Upjohn Spa | 2-Amino-thiazole derivatives, process for their preparation, and their use as antitumour agents |
-
2000
- 2000-07-26 US US09/616,629 patent/US6214852B1/en not_active Expired - Lifetime
- 2000-12-07 AT AT00982481T patent/ATE294800T1/de active
- 2000-12-07 ES ES00982481T patent/ES2241678T3/es not_active Expired - Lifetime
- 2000-12-07 CN CN00818899A patent/CN1433415A/zh active Pending
- 2000-12-07 CA CA002394544A patent/CA2394544A1/en not_active Abandoned
- 2000-12-07 CZ CZ20022013A patent/CZ20022013A3/cs unknown
- 2000-12-07 EE EEP200200306A patent/EE200200306A/xx unknown
- 2000-12-07 SI SI200020060A patent/SI20975B/sl not_active IP Right Cessation
- 2000-12-07 PL PL00364884A patent/PL364884A1/xx not_active Application Discontinuation
- 2000-12-07 KR KR1020027007617A patent/KR20020067547A/ko not_active Application Discontinuation
- 2000-12-07 AU AU19506/01A patent/AU774381B2/en not_active Ceased
- 2000-12-07 WO PCT/US2000/033113 patent/WO2001044241A1/en active Search and Examination
- 2000-12-07 EP EP00982481A patent/EP1240165B1/en not_active Expired - Lifetime
- 2000-12-07 PT PT00982481T patent/PT1240165E/pt unknown
- 2000-12-07 JP JP2001544731A patent/JP2003525872A/ja active Pending
- 2000-12-07 DE DE60019964T patent/DE60019964T2/de not_active Expired - Lifetime
- 2000-12-07 HU HU0300974A patent/HUP0300974A3/hu unknown
- 2000-12-07 DK DK00982481T patent/DK1240165T3/da active
- 2000-12-11 TW TW089126395A patent/TWI265930B/zh not_active IP Right Cessation
- 2000-12-14 CO CO00095239A patent/CO5251464A1/es not_active Application Discontinuation
- 2000-12-14 UY UY26480A patent/UY26480A1/es not_active Application Discontinuation
- 2000-12-15 PE PE2000001348A patent/PE20010932A1/es not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
DK1240165T3 (da) | 2005-08-08 |
ATE294800T1 (de) | 2005-05-15 |
TWI265930B (en) | 2006-11-11 |
CZ20022013A3 (cs) | 2003-03-12 |
CN1433415A (zh) | 2003-07-30 |
KR20020067547A (ko) | 2002-08-22 |
ES2241678T3 (es) | 2005-11-01 |
EE200200306A (et) | 2003-06-16 |
DE60019964D1 (en) | 2005-06-09 |
US6214852B1 (en) | 2001-04-10 |
CA2394544A1 (en) | 2001-06-21 |
AU774381B2 (en) | 2004-06-24 |
WO2001044241A1 (en) | 2001-06-21 |
EP1240165B1 (en) | 2005-05-04 |
SI20975B (sl) | 2006-04-30 |
AU1950601A (en) | 2001-06-25 |
UY26480A1 (es) | 2001-07-31 |
HUP0300974A2 (hu) | 2003-08-28 |
PT1240165E (pt) | 2005-09-30 |
SI20975A (sl) | 2003-02-28 |
HUP0300974A3 (en) | 2009-03-30 |
PL364884A1 (en) | 2004-12-27 |
JP2003525872A (ja) | 2003-09-02 |
DE60019964T2 (de) | 2006-04-27 |
EP1240165A1 (en) | 2002-09-18 |
PE20010932A1 (es) | 2001-11-18 |
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