HRP980368A2 - 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives - Google Patents
4-bromo or 4-iodo phenylamino benzhydroxamic acid derivativesInfo
- Publication number
- HRP980368A2 HRP980368A2 HR60/051,440A HRP980368A HRP980368A2 HR P980368 A2 HRP980368 A2 HR P980368A2 HR P980368 A HRP980368 A HR P980368A HR P980368 A2 HRP980368 A2 HR P980368A2
- Authority
- HR
- Croatia
- Prior art keywords
- phenylamino
- benzamide
- iodo
- difluoro
- methyl
- Prior art date
Links
- 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 4
- QAMBBWKIAJFFRF-UHFFFAOYSA-N n-hydroxy-2-(4-iodoanilino)benzamide Chemical class ONC(=O)C1=CC=CC=C1NC1=CC=C(I)C=C1 QAMBBWKIAJFFRF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 94
- -1 5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-[5-(3-methoxy-phenyl)-3-methyl-pent-2-ene-4-ynyloxy ]-benzamide Chemical compound 0.000 claims description 57
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 28
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 28
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 21
- 238000000034 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 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 230000002062 proliferating effect Effects 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 239000011737 fluorine Substances 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 208000037803 restenosis Diseases 0.000 claims description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 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 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 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 4
- LUAWFZQWIXYGPQ-UHFFFAOYSA-N 5-bromo-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1F LUAWFZQWIXYGPQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 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 description 3
- 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 description 3
- AAVSAALNWBQXSB-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-n-[2-(dimethylamino)ethoxy]-3,4-difluorobenzamide;hydrochloride Chemical compound Cl.CN(C)CCONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl AAVSAALNWBQXSB-UHFFFAOYSA-N 0.000 claims description 3
- YOURVUHYTAPYOX-UHFFFAOYSA-N 5-bromo-n-(cyclohexylmethoxy)-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCC1CCCCC1 YOURVUHYTAPYOX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 3
- BZJWSLFAFFNFIW-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Br BZJWSLFAFFNFIW-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- AVIWCXSGNKPKKK-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-chloro-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Br AVIWCXSGNKPKKK-UHFFFAOYSA-N 0.000 claims description 2
- JHBIWAOIBNORTA-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4,5-trifluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(F)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl JHBIWAOIBNORTA-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- SHNRDYXLGNJCOC-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-hydroxy-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NO)C(NC=2C(=CC(I)=CC=2)Cl)=C1 SHNRDYXLGNJCOC-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- RPWNJSYAWBWAFW-UHFFFAOYSA-N 5-bromo-2-(2-bromo-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Br RPWNJSYAWBWAFW-UHFFFAOYSA-N 0.000 claims description 2
- WBQVEORRHAMIPY-UHFFFAOYSA-N 5-bromo-n-(cyclobutylmethoxy)-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(Br)C=C1C(=O)NOCC1CCC1 WBQVEORRHAMIPY-UHFFFAOYSA-N 0.000 claims description 2
- MKRVIYRPNNYISB-UHFFFAOYSA-N 5-chloro-2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl MKRVIYRPNNYISB-UHFFFAOYSA-N 0.000 claims description 2
- FVMKNRIUORTHMN-UHFFFAOYSA-N 5-chloro-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F FVMKNRIUORTHMN-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 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
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- IVKQAKIJQNIBIO-UHFFFAOYSA-N n-hydroxy-2-(4-iodo-2-methylanilino)-4-nitrobenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC([N+]([O-])=O)=CC=C1C(=O)NO IVKQAKIJQNIBIO-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 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 2
- 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 2
- AYEUPCJRNJQNQD-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(oxan-2-yloxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOC1OCCCC1 AYEUPCJRNJQNQD-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- HHLZFIBFGYVDRZ-UHFFFAOYSA-N 5-chloro-n-hydroxy-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NO HHLZFIBFGYVDRZ-UHFFFAOYSA-N 0.000 claims 2
- UHAXDAKQGVISBZ-UHFFFAOYSA-N N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(F)C=C1C(=O)NOCC1CC1 UHAXDAKQGVISBZ-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
- KBJDNLWKCWKLMD-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-chloro-n-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C1CC1CONC(=O)C=1C=C(Cl)C(F)=C(F)C=1NC1=CC=C(I)C=C1Br KBJDNLWKCWKLMD-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
- RDTSNRQFNRNSCU-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Br)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 RDTSNRQFNRNSCU-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
- LHZVMSNGGDZKFO-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-(cyclopropylmethoxy)-4-nitrobenzamide Chemical compound C=1C=C(I)C=C(Br)C=1NC1=CC([N+](=O)[O-])=CC=C1C(=O)NOCC1CC1 LHZVMSNGGDZKFO-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
- 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
- YVSLCRVTJGUKSV-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4,5-trifluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC=1C(F)=C(F)C(F)=CC=1C(=O)NOCC1CC1 YVSLCRVTJGUKSV-UHFFFAOYSA-N 0.000 claims 1
- DVENTWJICBBDAJ-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-4-fluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=CC(F)=CC=C1C(=O)NOCC1CC1 DVENTWJICBBDAJ-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
- HDLXUSUTCIBXQZ-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(2-methylprop-2-enoxy)benzamide Chemical compound CC(=C)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C HDLXUSUTCIBXQZ-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
- HAONTWSXIVMMHV-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-(thiophen-2-ylmethoxy)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC1=CC=CS1 HAONTWSXIVMMHV-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
- FUDMVYZZNQDLOV-UHFFFAOYSA-N 3,4-difluoro-2-(4-iodo-2-methylanilino)-n-propoxybenzamide Chemical compound CCCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C FUDMVYZZNQDLOV-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
- OEYRWOJRMOBKSM-UHFFFAOYSA-N 3,4-difluoro-n-[3-(2-fluorophenyl)prop-2-ynoxy]-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=CC=C1C(=O)NOCC#CC1=CC=CC=C1F OEYRWOJRMOBKSM-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
- 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
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
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- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- POWOWTFZMKNONI-UHFFFAOYSA-N dilithium propan-2-olate Chemical compound [Li+].[Li+].CC(C)[O-].CC(C)[O-] POWOWTFZMKNONI-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000667 effect on insulin Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000006379 fluoropyridyl group Chemical group 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
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- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- HAUKUGBTJXWQMF-UHFFFAOYSA-N lithium;propan-2-olate Chemical compound [Li+].CC(C)[O-] HAUKUGBTJXWQMF-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 230000008747 mitogenic response Effects 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- FOGKWZGOCWAFPT-UHFFFAOYSA-N n-propan-2-yloxyethanamine Chemical compound CCNOC(C)C FOGKWZGOCWAFPT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003826 tablet 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
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl 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
- 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 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
- 230000000699 topical effect Effects 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
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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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)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Obesity (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 (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5144097P | 1997-07-01 | 1997-07-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP980368A2 true HRP980368A2 (en) | 1999-04-30 |
Family
ID=21971339
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR60/051,440A HRP980368A2 (en) | 1997-07-01 | 1998-06-30 | 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives |
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) |
Families Citing this family (106)
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 |
WO2000035435A1 (fr) * | 1998-12-15 | 2000-06-22 | Warner-Lambert Company | Technique de prevention du rejet de greffe par utilisation d'un inhibiteur du mek |
JP2002534381A (ja) * | 1999-01-07 | 2002-10-15 | ワーナー−ランバート・カンパニー | Mek阻害剤を用いた抗ウィルス法 |
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 |
ES2251851T3 (es) | 1999-01-13 | 2006-05-01 | Warner-Lambert Company Llc | Acidos sulfohidroxamicos y sulfohidroxamatos y su uso com inhibidores mek. |
NZ513433A (en) | 1999-01-13 | 2003-05-30 | Warner Lambert Co | Benzoheterocycles, their use as MEK inhibitors and use in treating proliferative diseases such as cancer |
CA2355374A1 (fr) * | 1999-01-13 | 2000-07-20 | Warner-Lambert Company | Diarylamines a substitution 1-heterocyclique |
WO2000042003A1 (fr) | 1999-01-13 | 2000-07-20 | Warner-Lambert Company | Derives de benzenesulfonamide et leur utilisation comme inhibiteurs de mek |
US6686499B1 (en) | 1999-04-21 | 2004-02-03 | Warner-Lambert Company | Method for making 2-(N-phenylamino)benzoic acids |
HUP0200932A3 (en) * | 1999-04-21 | 2002-11-28 | Warner Lambert Co | Method for making 2-(n-phenylamino)benzoic acids |
GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
TR200200082T2 (tr) * | 1999-07-16 | 2002-04-22 | Warner-Lambert Company | MEK inhibitörleri kullanılarak kronik ağrının tedavi edilmesi. |
US7001905B2 (en) | 2000-03-15 | 2006-02-21 | Warner-Lambert Company | Substituted diarylamines as MEK inhibitors |
AU2001247372A1 (en) * | 2000-03-15 | 2001-09-24 | Warner Lambert Company | 5-amide substituted diarylamines as mex inhibitors |
DE10017480A1 (de) * | 2000-04-07 | 2001-10-11 | Transmit Technologietransfer | Verwendung von Substanzen, die als MEK Inhibitor wirken, zur Herstellung eines Arneimittels gegen DNA- und RNA-Viren |
HU230251B1 (hu) * | 2000-07-19 | 2015-11-30 | Warner-Lambert Co. | 4-Jód-fenil-amino-benzhidroxámsav-észter-származékok és ezeket tartalmazó gyógyászati készítmények |
BR0113520A (pt) * | 2000-08-25 | 2003-06-24 | Warner Lambert Co | Processo de preparação de ácidos n-aril-antranìlicos e seus derivados |
US20020054869A1 (en) | 2000-09-01 | 2002-05-09 | Han-Mo Koo | Inhibition of mitogen-activated protein kinase (MAPK) pathway: a selective therapeutic strategy against melanoma |
US7253184B2 (en) | 2000-11-02 | 2007-08-07 | Astrazeneca Ab | 4-Substituted quinolines as antitumor agents |
US7067532B2 (en) | 2000-11-02 | 2006-06-27 | Astrazeneca | Substituted quinolines as antitumor agents |
WO2002076496A1 (fr) * | 2001-03-22 | 2002-10-03 | Van Andel Institute | Facteur letal de l'anthrax inhibant la croissance tumorale et l'angiogenese |
NZ518726A (en) * | 2001-05-09 | 2004-06-25 | Warner Lambert Co | Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor |
DOP2003000556A (es) | 2002-01-23 | 2003-10-31 | Warner Lambert Co | Esteres hidroxamato de acido n-(4-fenil-sustituido)-antranilico. |
WO2003062191A1 (fr) * | 2002-01-23 | 2003-07-31 | Warner-Lambert Company Llc | Esters hydroxamates d'acide n-(phenyl substitue en 4)-anthranilique |
PL401637A1 (pl) | 2002-03-13 | 2013-05-27 | Array Biopharma Inc. | N3 alkilowane pochodne benzimidazolu jako inhibitory MEK |
US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
ATE442847T1 (de) | 2003-07-24 | 2009-10-15 | Warner Lambert Co | Benzimidazol-derivate als mek-hemmer |
US7538120B2 (en) | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
EP1674452A4 (fr) | 2003-09-19 | 2007-10-10 | Chugai Pharmaceutical Co Ltd | Nouveau derive de 4-phenylamino-benzaldoxime et son utilisation en tant qu'inhibiteur de mek |
EP1682495A1 (fr) | 2003-10-21 | 2006-07-26 | Warner-Lambert Company LLC | Forme polymorphe du i n /i - (r)-2,3-dihydroxy-propoxy|-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-benzamide |
WO2005051302A2 (fr) | 2003-11-19 | 2005-06-09 | Array Biopharma Inc. | Inhibiteurs bicycliques de mek, et leurs procedes d'utilisation |
US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
CN1882347A (zh) | 2003-11-21 | 2006-12-20 | 阿雷生物药品公司 | Akt蛋白激酶抑制剂 |
UA89035C2 (ru) | 2003-12-03 | 2009-12-25 | Лео Фарма А/С | Эфиры гидроксамовых кислот и их фармацевтическое применение |
WO2005094830A1 (fr) * | 2004-03-30 | 2005-10-13 | Pfizer Products Inc. | Combinaisons d'inhibiteurs de transduction de signaux |
MY144232A (en) | 2004-07-26 | 2011-08-15 | Chugai Pharmaceutical Co Ltd | 5-substituted-2-phenylamino benzamides as mek inhibitors |
PL1781649T3 (pl) | 2004-08-17 | 2009-01-30 | Hoffmann La Roche | Podstawione hydantoiny |
TW200621766A (en) * | 2004-09-17 | 2006-07-01 | Hoffmann La Roche | Substituted hydantoins |
SI1802579T1 (sl) | 2004-10-20 | 2014-03-31 | Merck Serono Sa | Derivati 3-arilaminopiridina |
US8022247B2 (en) | 2005-04-06 | 2011-09-20 | Chugai Seiyaku Kabushiki Kaisha | Process for production of 2,3,4-trifluoro-5-(iodo or bromo)-benzoic acid |
EP1967516B1 (fr) | 2005-05-18 | 2009-11-04 | Array Biopharma, Inc. | Derivés 4-(phenylamino)-6-oxo-1,6-dihydropyridazine-3-carboxamide en tant que inhibiteurs MEK pour le traitement de maladies hyperproliferatives |
BRPI0617165B1 (pt) | 2005-10-07 | 2023-10-03 | Exelixis Inc | Compostos inibidores mek, composições farmacêuticas que os contem e métodos de uso dos mesmos |
US7612212B2 (en) | 2006-02-22 | 2009-11-03 | Hoffmann-La Roche Inc. | Substituted hydantoins |
WO2007132867A1 (fr) | 2006-05-15 | 2007-11-22 | Takeda Pharmaceutical Company Limited | Agent prophylactique et thérapeutique contre le cancer |
EP2054418B1 (fr) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothiéno pyrimidines comme inhibiteurs de la protéine kinase akt |
BRPI0713555A2 (pt) | 2006-07-06 | 2012-03-20 | Array Biopharma, Inc. | ciclopenta [d] pirimidinas como inibidores de akt protéina cinase |
US8329701B2 (en) | 2006-07-06 | 2012-12-11 | Array Biopharma Inc. | Dihydrofuro pyrimidines as AKT protein kinase inhibitors |
US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
EP1908751A1 (fr) * | 2006-10-03 | 2008-04-09 | EOS S.p.A. | Dérivés de N-hydroxybenzamide ayant une activité antitumorale |
EA200970407A1 (ru) | 2006-10-23 | 2009-12-30 | Такеда Фармасьютикал Компани Лимитед | Ингибиторы киназ mapk/erk |
CN111643496A (zh) | 2006-12-14 | 2020-09-11 | 埃克塞利希斯股份有限公司 | 使用mek抑制剂的方法 |
JPWO2008075741A1 (ja) * | 2006-12-20 | 2010-04-15 | 国立大学法人 長崎大学 | 糖尿病治療剤及び予防剤 |
AU2008272830B8 (en) | 2007-07-05 | 2013-12-12 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
CA2692506C (fr) | 2007-07-05 | 2015-11-24 | Array Biopharma Inc. | Pyrimidyl cyclopentanes utilses comme inhibiteurs de la proteine kinase akt |
US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
US7557221B2 (en) | 2007-08-16 | 2009-07-07 | Hoffman-La Roche Inc. | Substituted hydantoins |
AU2008341680A1 (en) | 2007-12-20 | 2009-07-02 | F. Hoffmann-La Roche Ag | Substituted hydantoins as MEK kinase inhibitors |
NZ586346A (en) | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
MX2010007546A (es) | 2008-01-09 | 2010-09-30 | Array Biopharma Inc | Pirimidil ciclopentanos hidroxilados en forma de inhibidores de akt proteína quinasa. |
WO2009143224A2 (fr) | 2008-05-20 | 2009-11-26 | Fox Chase Center Center | Procédé de traitement ou de prophylaxie d'une lymphangioléiomyomatose (lam) et modèle animal pour une utilisation dans la recherche sur la lam |
CA2732828C (fr) | 2008-08-04 | 2017-06-13 | Merck Patent Gmbh | Composes phenylamino isonicotinamides |
US8350026B2 (en) | 2008-08-27 | 2013-01-08 | Leo Pharma A/S | VEGF-2 receptor and protein tyrosine kinase inhibitors and pharmaceutical use thereof |
WO2010051933A2 (fr) | 2008-11-10 | 2010-05-14 | Bayer Schering Pharma Aktiengesellschaft | Sulfonamido phénoxybenzamides substitués |
EP2370568B1 (fr) | 2008-12-10 | 2017-07-19 | Dana-Farber Cancer Institute, Inc. | Mutations de mek conférant une résistance aux inhibiteurs de mek |
WO2011047796A1 (fr) | 2009-10-21 | 2011-04-28 | Bayer Schering Pharma Aktiengesellschaft | Dérivés d'halogénophénoxybenzamide substitués |
JP2013508318A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたベンゾスルホンアミド誘導体 |
CA2777430A1 (fr) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Benzosulfonamides substitues |
EP3028699B1 (fr) | 2010-02-25 | 2018-03-21 | Dana-Farber Cancer Institute, Inc. | Mutations braf conférant une résistance aux inhibiteurs de braf |
AU2011224410B2 (en) | 2010-03-09 | 2015-05-28 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
WO2012055953A1 (fr) | 2010-10-29 | 2012-05-03 | Bayer Pharma Aktiengesellschaft | Phénoxypyridines substituées |
JP6182456B2 (ja) | 2010-12-22 | 2017-08-23 | フェイト セラピューティクス,インコーポレイテッド | 単細胞選別のための細胞培養プラットホームおよびiPSCの再プログラミングの増強 |
CN103841976A (zh) | 2011-04-01 | 2014-06-04 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
HUE036513T2 (hu) | 2011-04-01 | 2018-07-30 | Genentech Inc | AKT inhibitor vegyület és abirateron kombinációja terápiás kezelésekben való alkalmazásra |
ES2597052T3 (es) | 2011-05-25 | 2017-01-13 | Université Paris Descartes | Inhibidores de ERK para su uso en el tratamiento de atrofia muscular espinal |
CN103204822B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
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 |
CN104837826B (zh) | 2012-10-12 | 2018-07-27 | 埃克塞里艾克西斯公司 | 制备用于治疗癌症的化合物的新型方法 |
WO2015038704A1 (fr) | 2013-09-11 | 2015-03-19 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Compositions pour prépaprer des cardiomyocytes |
EP3094736A4 (fr) | 2014-01-14 | 2017-10-25 | Dana-Farber Cancer Institute, Inc. | Compositions et méthodes pour l'identification, l'évaluation, la prévention, et le traitement d'un mélanome à l'aide d'isoformes de pd-l1 |
KR20240091064A (ko) | 2014-03-04 | 2024-06-21 | 페이트 세러퓨틱스, 인코포레이티드 | 개선된 재프로그래밍 방법 및 세포 배양 플랫폼 |
US10023879B2 (en) | 2014-06-04 | 2018-07-17 | Fate Therapeutics, Inc. | Minimal volume reprogramming of mononuclear cells |
CN105384754B (zh) * | 2014-09-02 | 2018-04-20 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的杂环类化合物及其制备方法和用途 |
US20170248603A1 (en) | 2014-10-06 | 2017-08-31 | Dana-Farber Cancer Institute, Inc. | Angiopoiten-2 biomarkers predictive of anti-immune checkpoint response |
US10626372B1 (en) | 2015-01-26 | 2020-04-21 | Fate Therapeutics, Inc. | Methods and compositions for inducing hematopoietic cell differentiation |
MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
CN117737124A (zh) | 2015-10-16 | 2024-03-22 | 菲特治疗公司 | 用于诱导和维护基态多能性的平台 |
EP4249074A3 (fr) | 2015-11-04 | 2024-01-10 | Fate Therapeutics, Inc. | Ingénierie génomique de cellules pluripotentes |
WO2017078807A1 (fr) | 2015-11-04 | 2017-05-11 | Fate Therapeutics, Inc. | Procédés et compositions pour induire la différenciation de cellules hématopoïétiques |
US11413309B2 (en) | 2016-01-20 | 2022-08-16 | Fate Therapeutics, Inc. | Compositions and methods for immune cell modulation in adoptive immunotherapies |
WO2017127729A1 (fr) | 2016-01-20 | 2017-07-27 | Fate Therapeutics, Inc. | Compositions et procédés permettant de moduler les cellules immunitaires en immunothérapies adoptives |
JP7194436B2 (ja) * | 2016-07-28 | 2022-12-22 | ザ ジョンズ ホプキンス ユニバーシティ | O-置換ヒドロキサム酸 |
JP7098615B2 (ja) | 2016-12-05 | 2022-07-11 | フェイト セラピューティクス,インコーポレイテッド | 養子免疫療法における免疫細胞調節のための組成物および方法 |
CN107556201B (zh) * | 2017-09-08 | 2020-10-27 | 山西智创药研科技有限公司 | 一种制备间氨基苯酚的工艺方法 |
CA3120352A1 (fr) * | 2018-11-20 | 2020-05-28 | Nflection Therapeutics, Inc. | Composes thienyl-aniline destines au traitement d'affections de la peau |
MA55143A (fr) * | 2018-11-20 | 2021-09-29 | H Lee Moffitt Cancer Center & Res Institute Inc | Composés aryl-aniline et hétéroaryl-aniline pour le traitement de cancers de la peau |
EP3942045A1 (fr) | 2019-03-21 | 2022-01-26 | Onxeo | Molécule dbait associée à un inhibiteur de kinase pour le traitement du cancer |
EP4054579A1 (fr) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Méthodes pour le traitement de cancers qui ont acquis une résistance aux inhibiteurs de kinase |
WO2021148581A1 (fr) | 2020-01-22 | 2021-07-29 | Onxeo | Nouvelle molécule dbait et son utilisation |
TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5525625A (en) * | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
AU5610398A (en) * | 1997-02-28 | 1998-09-18 | Warner-Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
-
1998
- 1998-06-24 HU HU0003731A patent/HUP0003731A3/hu unknown
- 1998-06-24 JP JP50722899A patent/JP2002511092A/ja not_active Abandoned
- 1998-06-24 CA CA002290506A patent/CA2290506C/fr not_active Expired - Fee Related
- 1998-06-24 DE DE69826662T patent/DE69826662T2/de not_active Expired - Lifetime
- 1998-06-24 WO PCT/US1998/013106 patent/WO1999001426A1/fr not_active Application Discontinuation
- 1998-06-24 BR BR9810366-0A patent/BR9810366A/pt not_active Application Discontinuation
- 1998-06-24 ES ES98932830T patent/ES2229515T3/es not_active Expired - Lifetime
- 1998-06-24 CN CNB988067501A patent/CN1163475C/zh not_active Expired - Fee Related
- 1998-06-24 AU AU82627/98A patent/AU757046B2/en not_active Ceased
- 1998-06-24 NZ NZ501276A patent/NZ501276A/xx unknown
- 1998-06-24 KR KR1019997012519A patent/KR20010014362A/ko not_active Application Discontinuation
- 1998-06-24 PT PT98932830T patent/PT993439E/pt unknown
- 1998-06-24 PL PL98337698A patent/PL337698A1/xx unknown
- 1998-06-24 EP EP98932830A patent/EP0993439B1/fr not_active Expired - Lifetime
- 1998-06-24 IL IL13284098A patent/IL132840A/en not_active IP Right Cessation
- 1998-06-24 AT AT98932830T patent/ATE277895T1/de not_active IP Right Cessation
- 1998-06-25 TW TW087110252A patent/TW396149B/zh not_active IP Right Cessation
- 1998-06-29 MY MYPI98002946A patent/MY120994A/en unknown
- 1998-06-30 AR ARP980103165A patent/AR016762A1/es unknown
- 1998-06-30 ZA ZA985728A patent/ZA985728B/xx unknown
- 1998-06-30 HR HR60/051,440A patent/HRP980368A2/hr not_active Application Discontinuation
- 1998-06-30 UY UY25076A patent/UY25076A1/es not_active Application Discontinuation
- 1998-06-30 CO CO98036883A patent/CO4940442A1/es unknown
- 1998-06-30 PE PE1998000579A patent/PE97999A1/es not_active Application Discontinuation
-
1999
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Also Published As
Publication number | Publication date |
---|---|
AU8262798A (en) | 1999-01-25 |
HUP0003731A2 (hu) | 2001-04-28 |
CO4940442A1 (es) | 2000-07-24 |
JP2002511092A (ja) | 2002-04-09 |
IL132840A0 (en) | 2001-03-19 |
NO996491D0 (no) | 1999-12-27 |
IS5256A (is) | 1999-11-19 |
DE69826662T2 (de) | 2005-02-17 |
WO1999001426A1 (fr) | 1999-01-14 |
PE97999A1 (es) | 1999-11-05 |
AU757046B2 (en) | 2003-01-30 |
ES2229515T3 (es) | 2005-04-16 |
CA2290506C (fr) | 2005-12-27 |
ZA985728B (en) | 1999-01-27 |
EP0993439A1 (fr) | 2000-04-19 |
TW396149B (en) | 2000-07-01 |
MY120994A (en) | 2005-12-30 |
NO996491L (no) | 1999-12-29 |
PL337698A1 (en) | 2000-08-28 |
NZ501276A (en) | 2000-10-27 |
CA2290506A1 (fr) | 1999-01-14 |
DE69826662D1 (de) | 2004-11-04 |
CN1261877A (zh) | 2000-08-02 |
NO315271B1 (no) | 2003-08-11 |
PT993439E (pt) | 2004-12-31 |
IL132840A (en) | 2004-12-15 |
CN1163475C (zh) | 2004-08-25 |
UY25076A1 (es) | 1998-12-01 |
EP0993439B1 (fr) | 2004-09-29 |
HUP0003731A3 (en) | 2002-11-28 |
AR016762A1 (es) | 2001-08-01 |
KR20010014362A (ko) | 2001-02-26 |
ATE277895T1 (de) | 2004-10-15 |
BR9810366A (pt) | 2000-08-29 |
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