CA2525325A1 - Pyrazole-amides et sulfonamides modulateurs des canaux sodiques - Google Patents
Pyrazole-amides et sulfonamides modulateurs des canaux sodiques Download PDFInfo
- Publication number
- CA2525325A1 CA2525325A1 CA002525325A CA2525325A CA2525325A1 CA 2525325 A1 CA2525325 A1 CA 2525325A1 CA 002525325 A CA002525325 A CA 002525325A CA 2525325 A CA2525325 A CA 2525325A CA 2525325 A1 CA2525325 A1 CA 2525325A1
- Authority
- CA
- Canada
- Prior art keywords
- aryl
- pyrazole
- carboxamide
- chlorophenyl
- heterocycle
- 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
- 108010052164 Sodium Channels Proteins 0.000 title description 9
- 102000018674 Sodium Channels Human genes 0.000 title description 9
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 title description 2
- 229940124530 sulfonamide Drugs 0.000 title description 2
- 150000003456 sulfonamides Chemical class 0.000 title 1
- -1 heterocyclealkyl Chemical group 0.000 claims abstract description 118
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 125000003118 aryl group Chemical group 0.000 claims abstract description 87
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 64
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 42
- 150000002148 esters Chemical class 0.000 claims abstract description 34
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 21
- 239000000651 prodrug Substances 0.000 claims abstract description 21
- 229940002612 prodrug Drugs 0.000 claims abstract description 21
- 150000001408 amides Chemical class 0.000 claims abstract description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
- 125000002947 alkylene group Chemical group 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 15
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000005138 alkoxysulfonyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000003725 azepanyl group Chemical group 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000004069 aziridinyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- ASHHDOZRIJQRJL-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-[(3,4-dichlorophenyl)methyl]-5-ethenylpyrazole-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1N1C(C=C)=C(C(=O)NCC=2C=C(Cl)C(Cl)=CC=2)C=N1 ASHHDOZRIJQRJL-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- JGYZWEZPCQPXPP-UHFFFAOYSA-N 1-(2-methoxyphenyl)-5-(trifluoromethyl)-n-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound COC1=CC=CC=C1N1C(C(F)(F)F)=C(C(=O)NCC=2C=C(C=CC=2)C(F)(F)F)C=N1 JGYZWEZPCQPXPP-UHFFFAOYSA-N 0.000 claims description 2
- BFMURVKMVVFJKJ-UHFFFAOYSA-N 1-(3-chlorophenyl)-n-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical group CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(N=C2)C=2C=C(Cl)C=CC=2)C(F)(F)F)=C1 BFMURVKMVVFJKJ-UHFFFAOYSA-N 0.000 claims description 2
- DRDPOYZYBHRVRE-UHFFFAOYSA-N 1-(3-methylphenyl)-n-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound CC1=CC=CC(N2C(=C(C(=O)NC=3C=C(C=CC=3)S(C)(=O)=O)C=N2)C(F)(F)F)=C1 DRDPOYZYBHRVRE-UHFFFAOYSA-N 0.000 claims description 2
- RBSLLFOKQBUWEH-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-cyano-n-(3-methylsulfonylphenyl)pyrazole-4-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(N=C2)C=2C=CC(Cl)=CC=2)C#N)=C1 RBSLLFOKQBUWEH-UHFFFAOYSA-N 0.000 claims description 2
- QKPUFGJCKMJLNB-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-ethenyl-n-(3-methylsulfonylphenyl)pyrazole-4-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(N=C2)C=2C=CC(Cl)=CC=2)C=C)=C1 QKPUFGJCKMJLNB-UHFFFAOYSA-N 0.000 claims description 2
- LQTAPLCRBFRTGD-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-methyl-n-(3-methylsulfonylphenyl)pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C=C(C=CC=2)S(C)(=O)=O)=NN1C1=CC=C(Cl)C=C1 LQTAPLCRBFRTGD-UHFFFAOYSA-N 0.000 claims description 2
- MCUPLZRVRSEOKE-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-methyl-n-[(2-methylphenyl)methyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NCC=2C(=CC=CC=2)C)=NN1C1=CC=C(Cl)C=C1 MCUPLZRVRSEOKE-UHFFFAOYSA-N 0.000 claims description 2
- SCBFDIAETJLQJO-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-methyl-n-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NCC=2C=C(C=CC=2)C(F)(F)F)=NN1C1=CC=C(Cl)C=C1 SCBFDIAETJLQJO-UHFFFAOYSA-N 0.000 claims description 2
- WVGKJUNXABIEFD-UHFFFAOYSA-N 1-(4-chlorophenyl)-5-methyl-n-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound CC1=C(C(=O)NCC=2C=C(C=CC=2)C(F)(F)F)C=NN1C1=CC=C(Cl)C=C1 WVGKJUNXABIEFD-UHFFFAOYSA-N 0.000 claims description 2
- JAGLKKAAKLQBKK-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-[2-(4-chlorophenyl)ethyl]-5-methylpyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NCCC=2C=CC(Cl)=CC=2)=NN1C1=CC=C(Cl)C=C1 JAGLKKAAKLQBKK-UHFFFAOYSA-N 0.000 claims description 2
- FMMRLSLPZXXZMR-UHFFFAOYSA-N 1-(4-methylphenyl)-n-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1N1C(C(F)(F)F)=C(C(=O)NC=2C=C(C=CC=2)S(C)(=O)=O)C=N1 FMMRLSLPZXXZMR-UHFFFAOYSA-N 0.000 claims description 2
- ZWSXQCVOQXBBPM-UHFFFAOYSA-N 1-cyclohexyl-5-(trifluoromethyl)-n-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound FC(F)(F)C1=C(C(=O)NCC=2C=C(C=CC=2)C(F)(F)F)C=NN1C1CCCCC1 ZWSXQCVOQXBBPM-UHFFFAOYSA-N 0.000 claims description 2
- MXFOCODSYBFVIE-UHFFFAOYSA-N 1-cyclohexyl-n-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(C3CCCCC3)N=C2)C(F)(F)F)=C1 MXFOCODSYBFVIE-UHFFFAOYSA-N 0.000 claims description 2
- MROAQIQXZDBAPJ-UHFFFAOYSA-N 5-acetyl-1-(4-chlorophenyl)-n-(3-methylsulfonylphenyl)pyrazole-4-carboxamide Chemical compound CC(=O)C1=C(C(=O)NC=2C=C(C=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(Cl)C=C1 MROAQIQXZDBAPJ-UHFFFAOYSA-N 0.000 claims description 2
- CBYCTWRBYNITAQ-UHFFFAOYSA-N 5-acetyl-1-(4-chlorophenyl)-n-[(3,4-dichlorophenyl)methyl]pyrazole-4-carboxamide Chemical compound CC(=O)C1=C(C(=O)NCC=2C=C(Cl)C(Cl)=CC=2)C=NN1C1=CC=C(Cl)C=C1 CBYCTWRBYNITAQ-UHFFFAOYSA-N 0.000 claims description 2
- RKFJCKLKGHCKND-UHFFFAOYSA-N CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(N=C2)C=2C=CC(Cl)=CC=2)O)=C1 Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(N=C2)C=2C=CC(Cl)=CC=2)O)=C1 RKFJCKLKGHCKND-UHFFFAOYSA-N 0.000 claims description 2
- OOXKNOOQJMJXCQ-UHFFFAOYSA-N OC1=C(C(=O)NCC=2C=CC=CC=2)C=NN1C1=CC=C(Cl)C=C1 Chemical compound OC1=C(C(=O)NCC=2C=CC=CC=2)C=NN1C1=CC=C(Cl)C=C1 OOXKNOOQJMJXCQ-UHFFFAOYSA-N 0.000 claims description 2
- ALWKDWPALYVVOG-UHFFFAOYSA-N n-[2-(4-chlorophenyl)ethyl]-1-(2-methoxyphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound COC1=CC=CC=C1N1C(C(F)(F)F)=C(C(=O)NCCC=2C=CC(Cl)=CC=2)C=N1 ALWKDWPALYVVOG-UHFFFAOYSA-N 0.000 claims description 2
- XXMLBLWSJWIIKM-UHFFFAOYSA-N n-[2-(4-chlorophenyl)ethyl]-1-(7-chloroquinolin-4-yl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=NN(C=2C3=CC=C(Cl)C=C3N=CC=2)C(C(F)(F)F)=C1C(=O)NCCC1=CC=C(Cl)C=C1 XXMLBLWSJWIIKM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- UHUKPORCSLIULB-UHFFFAOYSA-N 1-(1-benzylpiperidin-4-yl)-n-(3-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-4-carboxamide Chemical group CS(=O)(=O)C1=CC=CC(NC(=O)C2=C(N(C3CCN(CC=4C=CC=CC=4)CC3)N=C2)C(F)(F)F)=C1 UHUKPORCSLIULB-UHFFFAOYSA-N 0.000 claims 1
- IUKPHUWSBNDUBC-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-[(2-methoxyphenyl)methyl]-5-methylpyrazole-3-carboxamide Chemical compound COC1=CC=CC=C1CNC(=O)C1=NN(C=2C=CC(Cl)=CC=2)C(C)=C1 IUKPHUWSBNDUBC-UHFFFAOYSA-N 0.000 claims 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
- LMKAZJFNVXSZLM-UHFFFAOYSA-N [1-(4-chlorophenyl)-5-(trifluoromethyl)pyrazol-4-yl]-(4-cyclohexylpiperazin-1-yl)methanone Chemical group FC(F)(F)C1=C(C(=O)N2CCN(CC2)C2CCCCC2)C=NN1C1=CC=C(Cl)C=C1 LMKAZJFNVXSZLM-UHFFFAOYSA-N 0.000 claims 1
- CBFDSSQYDUWBCP-UHFFFAOYSA-N [4-(3-chlorophenyl)piperazin-1-yl]-[1-(4-chlorophenyl)-5-(trifluoromethyl)pyrazol-4-yl]methanone Chemical group FC(F)(F)C1=C(C(=O)N2CCN(CC2)C=2C=C(Cl)C=CC=2)C=NN1C1=CC=C(Cl)C=C1 CBFDSSQYDUWBCP-UHFFFAOYSA-N 0.000 claims 1
- FNWBWRHVMKSYAK-UHFFFAOYSA-N n-(1-benzylpiperidin-4-yl)-1-(4-chlorophenyl)-5-methylpyrazole-4-carboxamide Chemical group CC1=C(C(=O)NC2CCN(CC=3C=CC=CC=3)CC2)C=NN1C1=CC=C(Cl)C=C1 FNWBWRHVMKSYAK-UHFFFAOYSA-N 0.000 claims 1
- 208000002193 Pain Diseases 0.000 abstract description 13
- 241000124008 Mammalia Species 0.000 abstract description 11
- 230000036407 pain Effects 0.000 abstract description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 85
- 239000000047 product Substances 0.000 description 66
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- 239000000203 mixture Substances 0.000 description 39
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- 239000000243 solution Substances 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000002253 acid Substances 0.000 description 25
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 230000003197 catalytic effect Effects 0.000 description 12
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US10/427,847 | 2003-05-01 | ||
| US10/427,847 US20040220170A1 (en) | 2003-05-01 | 2003-05-01 | Pyrazole-amides and sulfonamides as sodium channel modulators |
| PCT/US2004/013530 WO2004099154A2 (fr) | 2003-05-01 | 2004-04-29 | Pyrazole-amides et sulfonamides modulateurs des canaux sodiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2525325A1 true CA2525325A1 (fr) | 2004-11-18 |
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ID=35529848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002525325A Abandoned CA2525325A1 (fr) | 2003-05-01 | 2004-04-29 | Pyrazole-amides et sulfonamides modulateurs des canaux sodiques |
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| EP (1) | EP1620405A2 (fr) |
| JP (1) | JP2006525355A (fr) |
| CA (1) | CA2525325A1 (fr) |
| MX (1) | MXPA05011775A (fr) |
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| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| US8183381B2 (en) * | 2007-07-19 | 2012-05-22 | Metabolex Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
| US8410127B2 (en) | 2009-10-01 | 2013-04-02 | Metabolex, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
| WO2012177263A1 (fr) * | 2011-06-24 | 2012-12-27 | Intra-Cellular Therapies, Inc. | Composés et procédés de prophylaxie et de traitement concernant des antagonistes de récepteur nicotinique |
| HUE040489T2 (hu) * | 2014-06-03 | 2019-03-28 | Idorsia Pharmaceuticals Ltd | Pirazolvegyületek és alkalmazásuk t-típusú kalciumcsatorna-blokkolókként |
| JP2019504840A (ja) * | 2016-01-28 | 2019-02-21 | ソルヴェイ（ソシエテ アノニム） | ハロゲン置換ジケトン、ピラゾール化合物およびピラゾール化合物の製造方法 |
| US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
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| ATE443698T1 (de) * | 1996-12-23 | 2009-10-15 | Bristol Myers Squibb Pharma Co | Stickstoffhaltige heterocyclen als faktor xa- hemmer |
| BR9810151A (pt) * | 1997-06-19 | 2000-08-08 | Du Pont Pharm Co | Composto, composição farmacêutica e método para tratamento ou prevenção de uma desordem tromoboembólica |
| IL136637A0 (en) * | 1997-12-22 | 2001-06-14 | Du Pont Pharm Co | Nitrogen containing heteroaromatics with ortho-substituted pi's as factor xa inhibitors |
| CA2373510A1 (fr) * | 1999-05-12 | 2000-11-23 | Ortho-Mcneil Pharmaceutical, Inc. | Carboxamides de pyrazole utiles pour le traitement de l'obesite et d'autres troubles |
| IL148698A0 (en) * | 1999-09-17 | 2002-09-12 | Cor Therapeutics Inc | INHIBITORS OF FACTOR Xa |
| CA2409827C (fr) * | 2000-05-22 | 2010-06-01 | Aventis Pharmaceuticals Products Inc. | Derives d'arylmethylamine utilises comme inhibiteurs de la tryptase |
| US6604974B2 (en) * | 2000-12-22 | 2003-08-12 | Thomson Licensing S.A. | Method and apparatus for applying crosswires to a tension focus mask |
| MXPA04012959A (es) * | 2002-06-29 | 2005-05-16 | Zentaris Gmbh | Arilcarbonilpiperacinas y heteroarilcarbonilpiperacinas y su uso para tratamiento de enfermedades de tumor benigno y maligno. |
| GB0226178D0 (en) * | 2002-11-11 | 2002-12-18 | Johnson Matthey Plc | Desulphurisation |
| AU2004218260A1 (en) * | 2003-01-28 | 2004-09-16 | Aventis Pharma S.A. | N-aryl heteroaromatic products, compositions containing same and use thereof |
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- 2004-04-29 MX MXPA05011775A patent/MXPA05011775A/es not_active Application Discontinuation
- 2004-04-29 CA CA002525325A patent/CA2525325A1/fr not_active Abandoned
- 2004-04-29 EP EP04751090A patent/EP1620405A2/fr not_active Withdrawn
- 2004-04-29 JP JP2006514200A patent/JP2006525355A/ja active Pending
Also Published As
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|---|---|
| EP1620405A2 (fr) | 2006-02-01 |
| MXPA05011775A (es) | 2006-02-17 |
| JP2006525355A (ja) | 2006-11-09 |
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| FZDE | Discontinued |