JP2010535233A5 - - Google Patents
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- Publication number
- JP2010535233A5 JP2010535233A5 JP2010520122A JP2010520122A JP2010535233A5 JP 2010535233 A5 JP2010535233 A5 JP 2010535233A5 JP 2010520122 A JP2010520122 A JP 2010520122A JP 2010520122 A JP2010520122 A JP 2010520122A JP 2010535233 A5 JP2010535233 A5 JP 2010535233A5
- Authority
- JP
- Japan
- Prior art keywords
- protein kinase
- kinase inhibitor
- combination
- alkyl
- mek
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000003909 protein kinase inhibitor Substances 0.000 claims 201
- 229940043355 kinase inhibitor Drugs 0.000 claims 194
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims 112
- -1 polymorph Chemical class 0.000 claims 101
- 239000003795 chemical substances by application Substances 0.000 claims 39
- 239000000460 chlorine Substances 0.000 claims 36
- 229910052801 chlorine Inorganic materials 0.000 claims 35
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims 34
- 229910052731 fluorine Inorganic materials 0.000 claims 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 34
- 229910052739 hydrogen Inorganic materials 0.000 claims 32
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims 30
- 229960003787 sorafenib Drugs 0.000 claims 30
- 230000006907 apoptotic process Effects 0.000 claims 27
- 230000004663 cell proliferation Effects 0.000 claims 26
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 150000001875 compounds Chemical class 0.000 claims 23
- 206010028980 Neoplasm Diseases 0.000 claims 20
- 201000011510 cancer Diseases 0.000 claims 20
- 150000002148 esters Chemical class 0.000 claims 20
- 239000000651 prodrug Substances 0.000 claims 20
- 229940002612 prodrug Drugs 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 20
- 239000012453 solvate Substances 0.000 claims 20
- 229910052794 bromium Inorganic materials 0.000 claims 19
- 229910052799 carbon Inorganic materials 0.000 claims 19
- 229910052736 halogen Inorganic materials 0.000 claims 19
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 17
- 150000002367 halogens Chemical class 0.000 claims 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 17
- 125000001424 substituent group Chemical group 0.000 claims 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 14
- 125000003118 aryl group Chemical group 0.000 claims 12
- 230000010261 cell growth Effects 0.000 claims 12
- 239000003112 inhibitor Substances 0.000 claims 12
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical group C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 10
- 229910052740 iodine Inorganic materials 0.000 claims 10
- 229910052757 nitrogen Inorganic materials 0.000 claims 10
- 229910052760 oxygen Inorganic materials 0.000 claims 10
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 claims 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims 9
- 125000005842 heteroatom Chemical group 0.000 claims 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 9
- 229920006395 saturated elastomer Polymers 0.000 claims 9
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 8
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 7
- 125000000304 alkynyl group Chemical group 0.000 claims 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- 102000004190 Enzymes Human genes 0.000 claims 6
- 108090000790 Enzymes Proteins 0.000 claims 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 6
- 230000000694 effects Effects 0.000 claims 6
- 125000001153 fluoro group Chemical group F* 0.000 claims 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims 5
- QXDAKFBVTWGQHQ-UHFFFAOYSA-N 2-nitroacetamide Chemical compound NC(=O)C[N+]([O-])=O QXDAKFBVTWGQHQ-UHFFFAOYSA-N 0.000 claims 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 5
- 125000003342 alkenyl group Chemical group 0.000 claims 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims 5
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 claims 4
- 101100381978 Mus musculus Braf gene Proteins 0.000 claims 4
- 102000001253 Protein Kinase Human genes 0.000 claims 4
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims 4
- 150000001408 amides Chemical class 0.000 claims 4
- 150000001412 amines Chemical class 0.000 claims 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 4
- 150000001721 carbon Chemical group 0.000 claims 4
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 229940080607 nexavar Drugs 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 4
- 108060006633 protein kinase Proteins 0.000 claims 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims 3
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims 3
- YABJJWZLRMPFSI-UHFFFAOYSA-N 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine Chemical compound N=1C2=CC(OC=3C=C(N=CC=3)C=3NC(=CN=3)C(F)(F)F)=CC=C2N(C)C=1NC1=CC=C(C(F)(F)F)C=C1 YABJJWZLRMPFSI-UHFFFAOYSA-N 0.000 claims 3
- 241000764238 Isis Species 0.000 claims 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 238000001727 in vivo Methods 0.000 claims 3
- OMEUGRCNAZNQLN-UHFFFAOYSA-N isis 5132 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(S)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)CO)C(O)C1 OMEUGRCNAZNQLN-UHFFFAOYSA-N 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical group C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims 2
- ZMSIFDIKIXVLDF-UHFFFAOYSA-N 2-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=CO1 ZMSIFDIKIXVLDF-UHFFFAOYSA-N 0.000 claims 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 108091034117 Oligonucleotide Proteins 0.000 claims 2
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 claims 2
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 claims 2
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims 2
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 238000011374 additional therapy Methods 0.000 claims 2
- 230000002411 adverse Effects 0.000 claims 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims 2
- 238000003782 apoptosis assay Methods 0.000 claims 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 2
- 150000001540 azides Chemical class 0.000 claims 2
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 238000001516 cell proliferation assay Methods 0.000 claims 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 claims 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 2
- 229960001285 quercetin Drugs 0.000 claims 2
- 235000005875 quercetin Nutrition 0.000 claims 2
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims 1
- RWEVIPRMPFNTLO-UHFFFAOYSA-N 2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-3-pyridinecarboxamide Chemical compound CN1C(=O)C(C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F RWEVIPRMPFNTLO-UHFFFAOYSA-N 0.000 claims 1
- RQSCFNPNNLWQBJ-UHFFFAOYSA-N 2-methyl-1,3,4-thiadiazole Chemical compound CC1=NN=CS1 RQSCFNPNNLWQBJ-UHFFFAOYSA-N 0.000 claims 1
- 101150019464 ARAF gene Proteins 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 201000004624 Dermatitis Diseases 0.000 claims 1
- 206010012735 Diarrhoea Diseases 0.000 claims 1
- 206010018001 Gastrointestinal perforation Diseases 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 108010066684 Proto-Oncogene Proteins A-raf Proteins 0.000 claims 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 claims 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 claims 1
- 208000031320 Teratogenesis Diseases 0.000 claims 1
- GSNOZLZNQMLSKJ-UHFFFAOYSA-N Trapidil Chemical compound CCN(CC)C1=CC(C)=NC2=NC=NN12 GSNOZLZNQMLSKJ-UHFFFAOYSA-N 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000004104 aryloxy group Chemical group 0.000 claims 1
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- BSMCAPRUBJMWDF-KRWDZBQOSA-N cobimetinib Chemical compound C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F BSMCAPRUBJMWDF-KRWDZBQOSA-N 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000890 drug combination Substances 0.000 claims 1
- 231100000351 embryotoxic Toxicity 0.000 claims 1
- 230000001779 embryotoxic effect Effects 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 235000020095 red wine Nutrition 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- 230000002195 synergetic effect Effects 0.000 claims 1
- 229960000363 trapidil Drugs 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
- 0 *c(cc1*)ccc1Nc1c(*)c(*)*(C=C)cc1NS(*)(=O)=O Chemical compound *c(cc1*)ccc1Nc1c(*)c(*)*(C=C)cc1NS(*)(=O)=O 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/830,733 | 2007-07-30 | ||
| US11/830,733 US8101799B2 (en) | 2005-07-21 | 2007-07-30 | Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK |
| US12/016,897 | 2008-01-18 | ||
| US12/016,897 US7820664B2 (en) | 2007-01-19 | 2008-01-18 | Inhibitors of MEK |
| PCT/US2008/071397 WO2009018238A1 (en) | 2007-07-30 | 2008-07-28 | Combinations of mek inhibitors and raf kinase inhibitors and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010535233A JP2010535233A (ja) | 2010-11-18 |
| JP2010535233A5 true JP2010535233A5 (enExample) | 2011-09-22 |
| JP5479337B2 JP5479337B2 (ja) | 2014-04-23 |
Family
ID=40304797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010520122A Expired - Fee Related JP5479337B2 (ja) | 2007-07-30 | 2008-07-28 | Ｍｅｋ阻害剤およびｒａｆキナーゼ阻害剤の組み合わせ、ならびにその使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8648116B2 (enExample) |
| EP (1) | EP2175885B1 (enExample) |
| JP (1) | JP5479337B2 (enExample) |
| CA (3) | CA2924436A1 (enExample) |
| UA (1) | UA99731C2 (enExample) |
| WO (1) | WO2009018238A1 (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4834553B2 (ja) | 2004-09-17 | 2011-12-14 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬組成物 |
| EP1925676A4 (en) | 2005-08-02 | 2010-11-10 | Eisai R&D Man Co Ltd | TEST METHOD FOR THE EFFECT OF A VASCULARIZATION INHIBITOR |
| CN101277720A (zh) * | 2005-09-01 | 2008-10-01 | 卫材R&D管理有限公司 | 崩解性被改善的药物组合物的制备方法 |
| US7723477B2 (en) | 2005-10-31 | 2010-05-25 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth |
| CA2652442C (en) | 2006-05-18 | 2014-12-09 | Eisai R & D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| US8044240B2 (en) * | 2008-03-06 | 2011-10-25 | Ardea Biosciences Inc. | Polymorphic form of N-(S)-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide and uses thereof |
| KR20110014149A (ko) * | 2008-04-14 | 2011-02-10 | 아디아 바이오사이언스즈 인크. | 조성물 및 이것의 제조 및 사용 방법 |
| CN102065859B (zh) * | 2008-06-13 | 2012-10-03 | 诺瓦提斯公司 | 用于神经纤维瘤病的取代的苯并咪唑类 |
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