JP2003528880A - 三環系タンパクキナーゼ阻害薬 - Google Patents
三環系タンパクキナーゼ阻害薬Info
- Publication number
- JP2003528880A JP2003528880A JP2001570667A JP2001570667A JP2003528880A JP 2003528880 A JP2003528880 A JP 2003528880A JP 2001570667 A JP2001570667 A JP 2001570667A JP 2001570667 A JP2001570667 A JP 2001570667A JP 2003528880 A JP2003528880 A JP 2003528880A
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- carbons
- alkyl
- carbon
- carboalkyl
- 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.)
- Pending
Links
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 185
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 208000030761 polycystic kidney disease Diseases 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 798
- -1 nitro, carboxy Chemical group 0.000 claims description 476
- 229910052757 nitrogen Inorganic materials 0.000 claims description 198
- 125000000217 alkyl group Chemical group 0.000 claims description 186
- 125000003118 aryl group Chemical group 0.000 claims description 139
- 229910052799 carbon Inorganic materials 0.000 claims description 126
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 114
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 112
- 125000000304 alkynyl group Chemical group 0.000 claims description 108
- 125000003342 alkenyl group Chemical group 0.000 claims description 107
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 105
- 239000000126 substance Substances 0.000 claims description 100
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 87
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 87
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 87
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 81
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 81
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 80
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 79
- 229910052736 halogen Inorganic materials 0.000 claims description 79
- 150000002367 halogens Chemical class 0.000 claims description 79
- 125000004970 halomethyl group Chemical group 0.000 claims description 79
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 79
- 125000001424 substituent group Chemical group 0.000 claims description 76
- 206010028980 Neoplasm Diseases 0.000 claims description 70
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 68
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 66
- 150000001540 azides Chemical class 0.000 claims description 66
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 66
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 66
- 125000003282 alkyl amino group Chemical group 0.000 claims description 65
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 56
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 54
- 125000004414 alkyl thio group Chemical group 0.000 claims description 53
- 125000004043 oxo group Chemical group O=* 0.000 claims description 52
- 125000004076 pyridyl group Chemical group 0.000 claims description 52
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 50
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 42
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 40
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 33
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 30
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 229920006395 saturated elastomer Polymers 0.000 claims description 30
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 27
- KPQGSZSWJWDQAV-UHFFFAOYSA-N C(#N)[C](C(=O)O)[N+](=O)[O-] Chemical compound C(#N)[C](C(=O)O)[N+](=O)[O-] KPQGSZSWJWDQAV-UHFFFAOYSA-N 0.000 claims description 26
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 230000002401 inhibitory effect Effects 0.000 claims description 21
- 230000037361 pathway Effects 0.000 claims description 21
- CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 claims description 21
- 241000124008 Mammalia Species 0.000 claims description 20
- 150000001721 carbon Chemical group 0.000 claims description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 17
- 230000001419 dependent effect Effects 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 15
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 15
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 15
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 230000012010 growth Effects 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
- 229930192474 thiophene Natural products 0.000 claims description 15
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 14
- 125000004754 (C2-C12) dialkylamino group Chemical group 0.000 claims description 14
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 14
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 14
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 14
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 14
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 14
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 14
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 14
- 150000003536 tetrazoles Chemical class 0.000 claims description 14
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 14
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 108091054455 MAP kinase family Proteins 0.000 claims description 13
- 102000043136 MAP kinase family Human genes 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000001589 carboacyl group Chemical group 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 150000003254 radicals Chemical class 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 13
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- 229940079593 drug Drugs 0.000 claims description 9
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- 229940043355 kinase inhibitor Drugs 0.000 claims description 5
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
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- 210000002429 large intestine Anatomy 0.000 claims description 4
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 4
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Neurology (AREA)
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- Ophthalmology & Optometry (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53691900A | 2000-03-28 | 2000-03-28 | |
| US09/536,919 | 2000-03-28 | ||
| PCT/US2001/010124 WO2001072758A1 (en) | 2000-03-28 | 2001-03-28 | Tricyclic protein kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003528880A true JP2003528880A (ja) | 2003-09-30 |
| JP2003528880A5 JP2003528880A5 (https=) | 2008-05-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001570667A Pending JP2003528880A (ja) | 2000-03-28 | 2001-03-28 | 三環系タンパクキナーゼ阻害薬 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1268487B1 (https=) |
| JP (1) | JP2003528880A (https=) |
| CN (1) | CN100369919C (https=) |
| AR (1) | AR028261A1 (https=) |
| AT (1) | ATE255114T1 (https=) |
| AU (1) | AU2001247882A1 (https=) |
| BR (1) | BR0109598A (https=) |
| CA (1) | CA2404445A1 (https=) |
| DE (1) | DE60101323T2 (https=) |
| MX (1) | MXPA02009440A (https=) |
| WO (1) | WO2001072758A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010539110A (ja) * | 2007-09-14 | 2010-12-16 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換三環式化合物およびその使用方法 |
| JP2013531016A (ja) * | 2010-07-14 | 2013-08-01 | ジャージャン ベータ ファーマ インコーポレイテッド | ｃ−ＭＥＴチロシンキナーゼ阻害薬として有用な新規な縮合複素環式誘導体 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2468015A1 (en) | 2001-11-27 | 2003-06-05 | Merck & Co., Inc. | 2-aminoquinoline compounds |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| BRPI0413018B8 (pt) | 2003-07-30 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, e, uso de um composto |
| KR20070011458A (ko) | 2004-04-08 | 2007-01-24 | 탈자진 인코포레이티드 | 키나제의 벤조트리아진 억제제 |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| WO2006133426A2 (en) | 2005-06-08 | 2006-12-14 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| CN103626742B (zh) | 2005-11-01 | 2017-04-26 | 塔格根公司 | 激酶的联-芳基间-嘧啶抑制剂 |
| CA2642229C (en) | 2006-02-24 | 2015-05-12 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US8309566B2 (en) | 2008-02-15 | 2012-11-13 | Rigel Pharmaceuticals, Inc. | Pyrimidine-2-amine compounds and their use as inhibitors of JAK kinases |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| MX2010011463A (es) | 2008-04-16 | 2011-06-03 | Portola Pharm Inc | 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas. |
| NZ588830A (en) | 2008-04-22 | 2012-11-30 | Portola Pharm Inc | Inhibitors of protein kinases |
| US9102625B2 (en) | 2010-11-01 | 2015-08-11 | Portola Pharmaceuticals, Inc. | Nicotinamides as JAK kinase modulators |
| CA2816957A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| CA3094793A1 (en) | 2011-11-23 | 2013-05-30 | Portola Pharmaceuticals, Inc. | Pyrazine kinase inhibitors |
| US9676756B2 (en) | 2012-10-08 | 2017-06-13 | Portola Pharmaceuticals, Inc. | Substituted pyrimidinyl kinase inhibitors |
| US20220143049A1 (en) | 2019-03-21 | 2022-05-12 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| WO2020245208A1 (en) | 2019-06-04 | 2020-12-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of cd9 as a biomarker and as a biotarget in glomerulonephritis or glomerulosclerosis |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2712290A1 (fr) * | 1993-11-10 | 1995-05-19 | Pf Medicament | Oxazino-acridines substituées, leur préparation et leur application en thérapeutique. |
| US6002008A (en) * | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
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2001
- 2001-03-16 AR ARP010101252A patent/AR028261A1/es unknown
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- 2001-03-28 JP JP2001570667A patent/JP2003528880A/ja active Pending
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- 2001-03-28 DE DE60101323T patent/DE60101323T2/de not_active Expired - Lifetime
- 2001-03-28 MX MXPA02009440A patent/MXPA02009440A/es active IP Right Grant
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010539110A (ja) * | 2007-09-14 | 2010-12-16 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | 置換三環式化合物およびその使用方法 |
| JP2013531016A (ja) * | 2010-07-14 | 2013-08-01 | ジャージャン ベータ ファーマ インコーポレイテッド | ｃ−ＭＥＴチロシンキナーゼ阻害薬として有用な新規な縮合複素環式誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001247882A1 (en) | 2001-10-08 |
| EP1268487B1 (en) | 2003-11-26 |
| BR0109598A (pt) | 2003-02-04 |
| DE60101323T2 (de) | 2004-05-27 |
| MXPA02009440A (es) | 2003-02-12 |
| EP1268487A1 (en) | 2003-01-02 |
| CA2404445A1 (en) | 2001-10-04 |
| WO2001072758A1 (en) | 2001-10-04 |
| CN100369919C (zh) | 2008-02-20 |
| ATE255114T1 (de) | 2003-12-15 |
| DE60101323D1 (de) | 2004-01-08 |
| CN1419559A (zh) | 2003-05-21 |
| AR028261A1 (es) | 2003-04-30 |
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