NO315271B1 - 4-brom- eller 4-jod-fenylamino-benzhydroksamsyrederivater, anvendelse deravog farmasöytiske preparater inneholdende dem - Google Patents
4-brom- eller 4-jod-fenylamino-benzhydroksamsyrederivater, anvendelse deravog farmasöytiske preparater inneholdende dem Download PDFInfo
- Publication number
- NO315271B1 NO315271B1 NO19996491A NO996491A NO315271B1 NO 315271 B1 NO315271 B1 NO 315271B1 NO 19996491 A NO19996491 A NO 19996491A NO 996491 A NO996491 A NO 996491A NO 315271 B1 NO315271 B1 NO 315271B1
- Authority
- NO
- Norway
- Prior art keywords
- benzamide
- difluoro
- iodo
- bromo
- methylphenylamino
- Prior art date
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- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 title description 3
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
- KOAYLMJFUSLPJI-UHFFFAOYSA-N 2-anilino-n-hydroxy-4-iodobenzamide Chemical class ONC(=O)C1=CC=C(I)C=C1NC1=CC=CC=C1 KOAYLMJFUSLPJI-UHFFFAOYSA-N 0.000 title 1
- -1 alkyl Chemical compound 0.000 claims abstract description 44
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 201000011510 cancer Diseases 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 230000002062 proliferating effect Effects 0.000 claims abstract description 15
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 10
- 208000037803 restenosis Diseases 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 107
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 40
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 27
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- HSDBAZASWXUUHX-UHFFFAOYSA-N 4-fluoro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NO HSDBAZASWXUUHX-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
- 208000006029 Cardiomegaly Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010019842 Hepatomegaly Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- VJNZMSLGVUSPCF-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C1CC1CONC(=O)C=1C=C(Br)C(F)=C(F)C=1NC1=CC=C(I)C=C1Cl VJNZMSLGVUSPCF-UHFFFAOYSA-N 0.000 claims 4
- SRMDAFUJVQJZFI-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl SRMDAFUJVQJZFI-UHFFFAOYSA-N 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- FVMCFMHLFMOYCO-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-(oxan-2-yloxy)benzamide Chemical compound C1CCCOC1ONC(=O)C=1C=C(Br)C(F)=C(F)C=1NC1=CC=C(I)C=C1Cl FVMCFMHLFMOYCO-UHFFFAOYSA-N 0.000 claims 2
- IBZPDAZZGTZKNJ-UHFFFAOYSA-N 5-bromo-n-[2-(dimethylamino)propoxy]-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CN(C)C(C)CONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1C IBZPDAZZGTZKNJ-UHFFFAOYSA-N 0.000 claims 2
- HPFQWCKXOZLYJQ-UHFFFAOYSA-N n-but-2-enoxy-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC=CCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C HPFQWCKXOZLYJQ-UHFFFAOYSA-N 0.000 claims 2
- ZHMSIFGQMCBYIY-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-3,4,5-trifluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(F)=C(F)C(F)=C1NC1=CC=C(I)C=C1Br ZHMSIFGQMCBYIY-UHFFFAOYSA-N 0.000 claims 1
- XYYUOXLXTADKMW-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-4-fluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1Br XYYUOXLXTADKMW-UHFFFAOYSA-N 0.000 claims 1
- BWOZEHCSZGOGER-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4,5-trifluorobenzamide Chemical compound C=1C=C(I)C=C(Br)C=1NC=1C(F)=C(F)C(F)=CC=1C(=O)NOCC1CC1 BWOZEHCSZGOGER-UHFFFAOYSA-N 0.000 claims 1
- LZRKJVJJXDFWLG-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-(cyclopropylmethoxy)-4-fluorobenzamide Chemical compound C=1C=C(I)C=C(Br)C=1NC1=CC(F)=CC=C1C(=O)NOCC1CC1 LZRKJVJJXDFWLG-UHFFFAOYSA-N 0.000 claims 1
- NMGPTKSLPIARAK-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-hydroxy-4-nitrobenzamide Chemical compound ONC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1Br NMGPTKSLPIARAK-UHFFFAOYSA-N 0.000 claims 1
- ZSOPSNFTRFGERY-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-(oxan-2-yloxy)benzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOC1CCCCO1 ZSOPSNFTRFGERY-UHFFFAOYSA-N 0.000 claims 1
- NXUSIIDZHWMSCV-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl NXUSIIDZHWMSCV-UHFFFAOYSA-N 0.000 claims 1
- IJCHFSDTDHLRIQ-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-4-fluoro-n-(oxan-2-yloxy)benzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=CC(F)=CC=C1C(=O)NOC1CCCCO1 IJCHFSDTDHLRIQ-UHFFFAOYSA-N 0.000 claims 1
- BZSLAYDTMNXEOY-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-4-fluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1Cl BZSLAYDTMNXEOY-UHFFFAOYSA-N 0.000 claims 1
- ROCRLSIAQQGIPN-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-(cyclobutylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CCC1 ROCRLSIAQQGIPN-UHFFFAOYSA-N 0.000 claims 1
- BOWUZVRUZUWLAM-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-ethoxy-4-nitrobenzamide Chemical compound CCONC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1Cl BOWUZVRUZUWLAM-UHFFFAOYSA-N 0.000 claims 1
- UUQXUOKQBSWOHD-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-hydroxy-4-nitrobenzamide Chemical compound ONC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1Cl UUQXUOKQBSWOHD-UHFFFAOYSA-N 0.000 claims 1
- UOPHVVWHOCFXFI-UHFFFAOYSA-N 2-(2-fluoro-4-iodoanilino)-n-hydroxy-4-nitrobenzamide Chemical compound ONC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1F UOPHVVWHOCFXFI-UHFFFAOYSA-N 0.000 claims 1
- BYNKDEUDKDVPPJ-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-methylprop-2-enoxy)benzamide Chemical compound CC(=C)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C BYNKDEUDKDVPPJ-UHFFFAOYSA-N 0.000 claims 1
- NITWKACUMSHLOB-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(2-phenoxyethoxy)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCCOC1=CC=CC=C1 NITWKACUMSHLOB-UHFFFAOYSA-N 0.000 claims 1
- DLCASGFAOPGKAH-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(3-phenylprop-2-ynoxy)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#CC1=CC=CC=C1 DLCASGFAOPGKAH-UHFFFAOYSA-N 0.000 claims 1
- YDOWUWRHGYWZHT-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-(furan-3-ylmethoxy)benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC1=COC=C1 YDOWUWRHGYWZHT-UHFFFAOYSA-N 0.000 claims 1
- MCDZEUZYVPGCQV-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-[3-(3-fluorophenyl)prop-2-ynoxy]benzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#CC1=CC=CC(F)=C1 MCDZEUZYVPGCQV-UHFFFAOYSA-N 0.000 claims 1
- WGIDTTDBLPTUHP-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-methoxybenzamide Chemical compound CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C WGIDTTDBLPTUHP-UHFFFAOYSA-N 0.000 claims 1
- LUDUVSBHPMEVQH-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-propan-2-yloxybenzamide Chemical compound CC(C)ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C LUDUVSBHPMEVQH-UHFFFAOYSA-N 0.000 claims 1
- HNXJNPOQVWVOGW-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-3,4-difluoro-n-propoxybenzamide Chemical compound CCCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C HNXJNPOQVWVOGW-UHFFFAOYSA-N 0.000 claims 1
- QTCFRZPPKGEZKF-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-(4,4-dimethylpent-2-ynoxy)-3,4-difluorobenzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#CC(C)(C)C QTCFRZPPKGEZKF-UHFFFAOYSA-N 0.000 claims 1
- BHEYIPCYQCTTAR-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 BHEYIPCYQCTTAR-UHFFFAOYSA-N 0.000 claims 1
- SLODYXNZAINLFD-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-but-2-enoxy-3,4-difluorobenzamide Chemical compound CC=CCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C SLODYXNZAINLFD-UHFFFAOYSA-N 0.000 claims 1
- LWZBCTIJTITZBA-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-but-3-ynoxy-3,4-difluorobenzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCCC#C LWZBCTIJTITZBA-UHFFFAOYSA-N 0.000 claims 1
- LUVODTHAYCCRJL-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-cyclobutyloxy-3,4-difluorobenzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOC1CCC1 LUVODTHAYCCRJL-UHFFFAOYSA-N 0.000 claims 1
- BZEJFQCJTPHNOF-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-cyclopentyloxy-3,4-difluorobenzamide Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOC1CCCC1 BZEJFQCJTPHNOF-UHFFFAOYSA-N 0.000 claims 1
- YDBKFXZLWHEYBN-UHFFFAOYSA-N 2-(4-bromo-2-methylanilino)-n-ethoxy-3,4-difluorobenzamide Chemical compound CCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(Br)C=C1C YDBKFXZLWHEYBN-UHFFFAOYSA-N 0.000 claims 1
- KGGHWIKBOIQEAJ-UHFFFAOYSA-N 2-fluorobenzamide Chemical compound NC(=O)C1=CC=CC=C1F KGGHWIKBOIQEAJ-UHFFFAOYSA-N 0.000 claims 1
- PYEBOHZEONEOFB-UHFFFAOYSA-N 3,4,5-trifluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(F)=C(F)C(F)=C1NC1=CC=C(I)C=C1F PYEBOHZEONEOFB-UHFFFAOYSA-N 0.000 claims 1
- CCYWUMAAAUNDJX-UHFFFAOYSA-N 3,4,5-trifluoro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(F)C=C1C(=O)NO CCYWUMAAAUNDJX-UHFFFAOYSA-N 0.000 claims 1
- HYIXUGDJHLKVGF-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-phenoxyethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCCOC1=CC=CC=C1 HYIXUGDJHLKVGF-UHFFFAOYSA-N 0.000 claims 1
- ILKRGOONQZFQPI-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(3-methyl-5-phenylpent-2-en-4-ynoxy)benzamide Chemical compound C=1C=CC=CC=1C#CC(C)=CCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C ILKRGOONQZFQPI-UHFFFAOYSA-N 0.000 claims 1
- RLUBNNSZZPDBIV-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(3-phenylprop-2-ynoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#CC1=CC=CC=C1 RLUBNNSZZPDBIV-UHFFFAOYSA-N 0.000 claims 1
- ZWXXSMYLKXWUIM-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-prop-2-ynoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#C ZWXXSMYLKXWUIM-UHFFFAOYSA-N 0.000 claims 1
- YPKLFSUXFMFTNP-UHFFFAOYSA-N 3,4-difluoro-n-(furan-3-ylmethoxy)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC1=COC=C1 YPKLFSUXFMFTNP-UHFFFAOYSA-N 0.000 claims 1
- ILYBIGUHBUIMMX-UHFFFAOYSA-N 3,4-difluoro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NO ILYBIGUHBUIMMX-UHFFFAOYSA-N 0.000 claims 1
- OFJHKJAWPYMKAO-UHFFFAOYSA-N 4-bromo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(Br)=CC=C1C(=O)NOCC1=CC=CC=C1 OFJHKJAWPYMKAO-UHFFFAOYSA-N 0.000 claims 1
- OEDQBUOUDGINPB-UHFFFAOYSA-N 4-fluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1F OEDQBUOUDGINPB-UHFFFAOYSA-N 0.000 claims 1
- XYPDOWBXGOOEOA-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(2-phenoxyethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCCOC1=CC=CC=C1 XYPDOWBXGOOEOA-UHFFFAOYSA-N 0.000 claims 1
- PBAMOEUDSFIDGM-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-(thiophen-2-ylmethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC1=CC=CS1 PBAMOEUDSFIDGM-UHFFFAOYSA-N 0.000 claims 1
- PEZQORQECWUYJA-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-methoxybenzamide Chemical compound CONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C PEZQORQECWUYJA-UHFFFAOYSA-N 0.000 claims 1
- IVJXLCPTSRJPLQ-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC1=CC=CC=C1 IVJXLCPTSRJPLQ-UHFFFAOYSA-N 0.000 claims 1
- PFWAYQMMRCDJJX-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-prop-2-enoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC=C PFWAYQMMRCDJJX-UHFFFAOYSA-N 0.000 claims 1
- VFLRZRPXLGMONP-UHFFFAOYSA-N 4-fluoro-2-(4-iodo-2-methylanilino)-n-prop-2-ynoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=CC=C1C(=O)NOCC#C VFLRZRPXLGMONP-UHFFFAOYSA-N 0.000 claims 1
- TYSFIFCGLKBEJN-UHFFFAOYSA-N 4-fluoro-n-hydroxy-2-(4-iodo-2-methylanilino)-5-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC(F)=C([N+]([O-])=O)C=C1C(=O)NO TYSFIFCGLKBEJN-UHFFFAOYSA-N 0.000 claims 1
- DPWYBHGUHGHXDP-UHFFFAOYSA-N 4-fluoro-n-hydroxy-2-(4-iodo-2-methylanilino)-n-methylbenzamide Chemical compound CN(O)C(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C DPWYBHGUHGHXDP-UHFFFAOYSA-N 0.000 claims 1
- GRGWLBCAWYUDDI-UHFFFAOYSA-N 4-fluoro-n-hydroxy-2-(4-iodo-2-methylanilino)-n-propan-2-ylbenzamide Chemical compound CC(C)N(O)C(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1C GRGWLBCAWYUDDI-UHFFFAOYSA-N 0.000 claims 1
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- 238000004949 mass spectrometry Methods 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
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- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
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- 229940092253 ovalbumin Drugs 0.000 description 1
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- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
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- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- KHVCOYGKHDJPBZ-WDCZJNDASA-N tetrahydrooxazine Chemical compound OC[C@H]1ONC[C@@H](O)[C@@H]1O KHVCOYGKHDJPBZ-WDCZJNDASA-N 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
- C07D309/06—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5144097P | 1997-07-01 | 1997-07-01 | |
PCT/US1998/013106 WO1999001426A1 (fr) | 1997-07-01 | 1998-06-24 | Derives d'acide benzhydroxamique phenylamino 4-bromo ou 4-iodo et utilisation de ces derniers en tant qu'inhibiteurs de mek |
Publications (3)
Publication Number | Publication Date |
---|---|
NO996491D0 NO996491D0 (no) | 1999-12-27 |
NO996491L NO996491L (no) | 1999-12-29 |
NO315271B1 true NO315271B1 (no) | 2003-08-11 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19996491A NO315271B1 (no) | 1997-07-01 | 1999-12-27 | 4-brom- eller 4-jod-fenylamino-benzhydroksamsyrederivater, anvendelse deravog farmasöytiske preparater inneholdende dem |
Country Status (26)
Country | Link |
---|---|
EP (1) | EP0993439B1 (fr) |
JP (1) | JP2002511092A (fr) |
KR (1) | KR20010014362A (fr) |
CN (1) | CN1163475C (fr) |
AR (1) | AR016762A1 (fr) |
AT (1) | ATE277895T1 (fr) |
AU (1) | AU757046B2 (fr) |
BR (1) | BR9810366A (fr) |
CA (1) | CA2290506C (fr) |
CO (1) | CO4940442A1 (fr) |
DE (1) | DE69826662T2 (fr) |
ES (1) | ES2229515T3 (fr) |
HR (1) | HRP980368A2 (fr) |
HU (1) | HUP0003731A3 (fr) |
IL (1) | IL132840A (fr) |
IS (1) | IS5256A (fr) |
MY (1) | MY120994A (fr) |
NO (1) | NO315271B1 (fr) |
NZ (1) | NZ501276A (fr) |
PE (1) | PE97999A1 (fr) |
PL (1) | PL337698A1 (fr) |
PT (1) | PT993439E (fr) |
TW (1) | TW396149B (fr) |
UY (1) | UY25076A1 (fr) |
WO (1) | WO1999001426A1 (fr) |
ZA (1) | ZA985728B (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011106298A1 (fr) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Mutations de braf conférant une résistance aux inhibiteurs de braf |
WO2013169858A1 (fr) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Méthodes de diagnostic et de traitement chez des patients ayant ou présentant un risque de développer une résistance à une thérapie anticancéreuse |
Families Citing this family (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6506798B1 (en) | 1997-07-01 | 2003-01-14 | Warner-Lambert Company | 4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors |
US6846799B1 (en) | 1998-08-18 | 2005-01-25 | The Regents Of The University Of California | Preventing airway mucus production by administration of EGF-R antagonists |
US7354894B2 (en) | 1998-08-18 | 2008-04-08 | The Regents Of The University Of California | Preventing airway mucus production by administration of EGF-R antagonists |
EP1140046A1 (fr) * | 1998-12-15 | 2001-10-10 | Warner-Lambert Company | Technique de prevention du rejet de greffe par utilisation d'un inhibiteur du mek |
CA2358438A1 (fr) * | 1999-01-07 | 2000-07-13 | David Thomas Dudley | Methode antivirale utilisant des inhibiteurs de mek |
SK9832001A3 (en) | 1999-01-13 | 2003-02-04 | Warner Lambert Co | Benzoheterocycles and their use as MEK inhibitors |
KR20010108093A (ko) | 1999-01-13 | 2001-12-07 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | 1-헤테로고리 치환된 디아릴아민 |
CA2348236A1 (fr) * | 1999-01-13 | 2000-07-20 | Stephen Douglas Barrett | 4-arylamino, 4-aryloxy, et 4-arylthio diarylamines et leurs derives comme inhibiteurs selectifs de mek |
BR9916894A (pt) | 1999-01-13 | 2001-11-20 | Warner Lambert Co | ácidos sulfohidroxâmicos e sulfohidroxamatos eseu uso como inibidores de mek |
DE69928286T2 (de) | 1999-01-13 | 2006-07-13 | Warner-Lambert Co. Llc | Benzenesulfonamid-derivative und ihre verwendung als mek-inhibitoren |
US6686499B1 (en) | 1999-04-21 | 2004-02-03 | Warner-Lambert Company | Method for making 2-(N-phenylamino)benzoic acids |
GEP20033089B (en) * | 1999-04-21 | 2003-10-27 | Warner Lambert Co | Method for Making 2-(N-Phenyl-amino) Benzoic Acids |
GB9910579D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
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1998
- 1998-06-24 BR BR9810366-0A patent/BR9810366A/pt not_active Application Discontinuation
- 1998-06-24 PL PL98337698A patent/PL337698A1/xx unknown
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Cited By (2)
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WO2011106298A1 (fr) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Mutations de braf conférant une résistance aux inhibiteurs de braf |
WO2013169858A1 (fr) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Méthodes de diagnostic et de traitement chez des patients ayant ou présentant un risque de développer une résistance à une thérapie anticancéreuse |
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HUP0003731A2 (hu) | 2001-04-28 |
ES2229515T3 (es) | 2005-04-16 |
CA2290506A1 (fr) | 1999-01-14 |
CO4940442A1 (es) | 2000-07-24 |
UY25076A1 (es) | 1998-12-01 |
AU757046B2 (en) | 2003-01-30 |
CN1163475C (zh) | 2004-08-25 |
AR016762A1 (es) | 2001-08-01 |
CN1261877A (zh) | 2000-08-02 |
NO996491L (no) | 1999-12-29 |
EP0993439A1 (fr) | 2000-04-19 |
PT993439E (pt) | 2004-12-31 |
ZA985728B (en) | 1999-01-27 |
WO1999001426A1 (fr) | 1999-01-14 |
HRP980368A2 (en) | 1999-04-30 |
KR20010014362A (ko) | 2001-02-26 |
JP2002511092A (ja) | 2002-04-09 |
TW396149B (en) | 2000-07-01 |
DE69826662D1 (de) | 2004-11-04 |
AU8262798A (en) | 1999-01-25 |
ATE277895T1 (de) | 2004-10-15 |
EP0993439B1 (fr) | 2004-09-29 |
HUP0003731A3 (en) | 2002-11-28 |
NZ501276A (en) | 2000-10-27 |
NO996491D0 (no) | 1999-12-27 |
MY120994A (en) | 2005-12-30 |
BR9810366A (pt) | 2000-08-29 |
PL337698A1 (en) | 2000-08-28 |
IL132840A (en) | 2004-12-15 |
IS5256A (is) | 1999-11-19 |
IL132840A0 (en) | 2001-03-19 |
CA2290506C (fr) | 2005-12-27 |
DE69826662T2 (de) | 2005-02-17 |
PE97999A1 (es) | 1999-11-05 |
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