JP2010535233A5 - - Google Patents
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- 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) | CA2924418A1 (enExample) |
| UA (1) | UA99731C2 (enExample) |
| WO (1) | WO2009018238A1 (enExample) |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1797881B1 (en) | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| WO2007015578A1 (ja) | 2005-08-02 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を検定する方法 |
| EP1938842A4 (en) * | 2005-09-01 | 2013-01-09 | Eisai R&D Man Co Ltd | METHOD FOR PRODUCING A PHARMACEUTICAL COMPOSITION COMPRISING IMPROVED CRASHING CHARACTERISTICS |
| US7723477B2 (en) | 2005-10-31 | 2010-05-25 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth |
| ES2556173T3 (es) | 2006-05-18 | 2016-01-13 | Eisai R&D Management Co., Ltd. | Agente antitumoral para un cáncer de tiroides |
| 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 |
| EP2291350A4 (en) * | 2008-04-14 | 2012-09-19 | Ardea Biosciences Inc | COMPOSITIONS AND METHODS FOR THEIR MANUFACTURE AND USE |
| WO2009152288A1 (en) * | 2008-06-13 | 2009-12-17 | Novartis Ag | Substituted benzimidazoles for neurofibromatosis |
| BRPI0919473A2 (pt) | 2008-09-26 | 2017-08-29 | Oncomed Pharm Inc | Agentes de ligação frizzled e usos dos mesmos |
| PE20120105A1 (es) * | 2009-03-11 | 2012-02-22 | Ardea Biosciences Inc | Combinaciones farmaceuticas que comprenden refametinib |
| TWI524890B (zh) | 2009-07-24 | 2016-03-11 | 亞德生化公司 | （ｒ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺及（ｓ）－ｎ－（３，４－二氟－２－（２－氟－４－碘苯胺基）－６－甲氧基苯基）－１－（２，３－二羥丙基）環丙烷－１－磺醯胺之製備 |
| WO2011044072A1 (en) * | 2009-10-05 | 2011-04-14 | Novartis Ag | Combination of raf-265 and an activator of ampk for use in the treatment of a proliferative disease |
| CN102666512B (zh) | 2009-10-13 | 2014-11-26 | 奥斯特姆医疗公司 | 对疾病治疗有用的mek抑制剂 |
| ES2745479T3 (es) | 2009-10-16 | 2020-03-02 | Novartis Ag | Combinación que comprende un inhibidor de MEK y un inhibidor de B-raf |
| MX2012005293A (es) | 2009-11-04 | 2012-06-19 | Novartis Ag | Derivados de sulfonamida heterociclicos utiles como inhibidores de mek. |
| CA2991896A1 (en) | 2009-12-01 | 2011-06-09 | Abbvie Inc. | Novel tricyclic compounds as protein kinase inhibitors |
| TWI535445B (zh) | 2010-01-12 | 2016-06-01 | 安可美德藥物股份有限公司 | Ｗｎｔ拮抗劑及治療和篩選方法 |
| BR112012022801B8 (pt) * | 2010-03-09 | 2019-10-29 | Dana Farber Cancer Inst Inc | método de identificar um indivíduo que tem câncer que é provável beneficiar-se do tratamento com uma terapia de combinação com um inibidor de raf e um segundo inibidor e uso de um inibidor de raf e um segundo inibidor para a fabricação de um medicamento para tratar câncer |
| CA2813069A1 (en) * | 2010-10-01 | 2012-04-05 | Bayer Intellectual Property Gmbh | Substituted n-(2-arylamino)aryl sulfonamide-containing combinations |
| CN102020651B (zh) | 2010-11-02 | 2012-07-18 | 北京赛林泰医药技术有限公司 | 6-芳基氨基吡啶酮甲酰胺mek抑制剂 |
| WO2012061683A2 (en) * | 2010-11-05 | 2012-05-10 | Glaxosmithkline Llc | Methods for treating cancer |
| TWI505828B (zh) * | 2010-12-20 | 2015-11-01 | 葛蘭素史克智慧財產（第二）有限公司 | 新穎醫藥組成物 |
| RU2580609C2 (ru) * | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
| WO2012145503A1 (en) * | 2011-04-21 | 2012-10-26 | Novartis Ag | Pharmaceutical combinations |
| EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| DE102011104267A1 (de) * | 2011-06-06 | 2012-12-06 | Philipps-Universität Marburg | Verbindungen als PPAR beta/delta Inhibitoren für die Behandlung von PPAR beta/delta-vermittelten Erkrankungen |
| CN103748085A (zh) | 2011-06-09 | 2014-04-23 | 诺华股份有限公司 | 杂环磺酰胺衍生物 |
| JP2014517004A (ja) * | 2011-06-09 | 2014-07-17 | ノバルティス アーゲー | 複素環スルホンアミド誘導体 |
| WO2013086260A2 (en) * | 2011-12-09 | 2013-06-13 | Oncomed Pharmaceuticals, Inc. | Combination therapy for treatment of cancer |
| EP2796455A4 (en) * | 2011-12-19 | 2015-08-19 | Sumitomo Chemical Co | PROCESS FOR THE PREPARATION OF SULPHONATE |
| WO2013109142A1 (en) | 2012-01-16 | 2013-07-25 | Stichting Het Nederlands Kanker Instituut | Combined pdk and mapk/erk pathway inhibition in neoplasia |
| CN103204825B (zh) | 2012-01-17 | 2015-03-04 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 |
| US20150267258A1 (en) * | 2012-05-31 | 2015-09-24 | Bayer Pharma Aktiengesellschaft | Biomarkers for determining effective response of treatments of hepatocellular carcinoma (hcc) patients |
| RS59113B1 (sr) | 2012-08-17 | 2019-09-30 | Hoffmann La Roche | Kombinovane terapije za melanom koje uključuju davanje kobimetiniba i vemurafiniba |
| CA2890238A1 (en) | 2012-11-02 | 2014-05-08 | Merck Patent Gmbh | Method of reducing adverse effects in a cancer patient undergoing treatment with a mek inhibitor |
| AU2013364953A1 (en) | 2012-12-21 | 2015-04-30 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| CN105073195A (zh) | 2013-02-04 | 2015-11-18 | 昂科梅德制药有限公司 | 使用Wnt途径抑制剂进行治疗的方法及对该治疗的监测 |
| WO2014185540A1 (en) | 2013-05-14 | 2014-11-20 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| HUE035877T2 (en) * | 2013-09-13 | 2018-05-28 | Bayer Pharma AG | Pharmaceutical preparations containing Refametinib |
| EP2848246A1 (en) | 2013-09-13 | 2015-03-18 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
| US9629851B2 (en) | 2013-09-20 | 2017-04-25 | Stitching Het Nederlands Kanker Institut—Antoni Van Leeuwenhoek Ziekenhuis | ROCK in combination with MAPK pathway |
| WO2015041534A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | P90rsk in combination with raf/erk/mek |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| WO2015178770A1 (en) | 2014-05-19 | 2015-11-26 | Stichting Het Nederlands Kanker Instituut | Compositions for cancer treatment |
| JP2017517552A (ja) * | 2014-06-13 | 2017-06-29 | ジェネンテック， インコーポレイテッド | 抗癌剤耐性の治療及び防止方法 |
| WO2015196072A2 (en) | 2014-06-19 | 2015-12-23 | Whitehead Institute For Biomedical Research | Uses of kinase inhibitors for inducing and maintaining pluripotency |
| KR102329681B1 (ko) | 2014-08-28 | 2021-11-23 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 고순도의 퀴놀린 유도체 및 이를 제조하는 방법 |
| EP3222276B1 (en) * | 2014-11-19 | 2021-04-07 | National Defense Medical Center | Pharmaceutical composition for treating cancer and biomarker for drug screening |
| US20190117652A1 (en) * | 2014-12-23 | 2019-04-25 | Millennium Pharmaceuticals, Inc. | Combination of raf inhibitors and taxanes |
| KR20250024102A (ko) | 2015-02-25 | 2025-02-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 고미 억제 방법 |
| AU2015384801B2 (en) | 2015-03-04 | 2022-01-06 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| ES2886107T3 (es) | 2015-06-16 | 2021-12-16 | Prism Biolab Co Ltd | Antineoplásico |
| SG11201801083UA (en) | 2015-08-20 | 2018-03-28 | Eisai R&D Man Co Ltd | Tumor therapeutic agent |
| WO2017033113A1 (en) | 2015-08-21 | 2017-03-02 | Acerta Pharma B.V. | Therapeutic combinations of a mek inhibitor and a btk inhibitor |
| JP7037500B2 (ja) * | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Ｍｄｍ２タンパク質分解剤 |
| WO2018107146A1 (en) * | 2016-12-11 | 2018-06-14 | Memorial Sloan Kettering Cancer Center | Methods and compositions for treatment of braf mutant cancers |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| US20200197384A1 (en) | 2017-05-16 | 2020-06-25 | Eisai R&D Management Co., Ltd. | Treatment of hepatocellular carcinoma |
| US11311624B2 (en) | 2017-08-11 | 2022-04-26 | The Regents Of The University Of Michigan | Inhibitors of MEK/PI3K, JAK/MEK, JAK/PI3K/mTOR and MEK/PI3K/mTOR biological pathways and methods for improving lymphatic uptake, bioavailability, and solubility of therapeutic compounds |
| US11559544B2 (en) | 2017-08-23 | 2023-01-24 | Cell Receptor AG | Combination of a MAPK/ERK pathway inhibitor and a glycosaminoglycan for the treatment of cancer |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR102275782B1 (ko) * | 2019-06-18 | 2021-07-09 | 주식회사 스탠다임 | 대사성 간질환의 예방 또는 치료용 조성물 |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| US12371667B2 (en) | 2021-05-13 | 2025-07-29 | Washington University | Enhanced methods for inducing and maintaining naive human pluripotent stem cells |
| JP2024521788A (ja) | 2021-05-27 | 2024-06-04 | ミラティ セラピューティクス， インコーポレイテッド | 併用療法 |
| WO2025073765A1 (en) | 2023-10-03 | 2025-04-10 | Institut National de la Santé et de la Recherche Médicale | Methods of prognosis and treatment of patients suffering from melanoma |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5744362A (en) * | 1994-05-31 | 1998-04-28 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| FI973974A7 (fi) | 1995-04-20 | 1997-10-16 | Pfizer | Aryylisulfonyylihydroksaamihappojohdannaisia MMP- ja TNF-inhibiittorei na |
| DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| HUP9903014A3 (en) | 1996-07-18 | 2000-08-28 | Pfizer | Phosphinate derivatives having matrix metalloprotease inhibitor effect and medicaments containing the same |
| IL128189A0 (en) | 1996-08-23 | 1999-11-30 | Pfizer | Arylsulfonylamino hydroxamic acid derivatives |
| ES2224277T3 (es) | 1997-01-06 | 2005-03-01 | Pfizer Inc. | Derivados de sulfonas ciclicas. |
| PT977733E (pt) | 1997-02-03 | 2003-12-31 | Pfizer Prod Inc | Derivados de acido arilsulfonilamino-hidroxamico |
| JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
| IL131123A0 (en) | 1997-02-11 | 2001-01-28 | Pfizer | Arylsulfonyl hydroxamic acid derivatives |
| US7115632B1 (en) * | 1999-05-12 | 2006-10-03 | G. D. Searle & Co. | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
| US6310060B1 (en) | 1998-06-24 | 2001-10-30 | Warner-Lambert Company | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| US20040171632A1 (en) * | 1998-12-22 | 2004-09-02 | Gowan Richard Carleton | Combination chemotherapy |
| IL144215A0 (en) * | 1999-01-13 | 2002-05-23 | Warner Lambert Co | 1-heterocycle substituted diarylamines |
| US6316462B1 (en) * | 1999-04-09 | 2001-11-13 | Schering Corporation | Methods of inducing cancer cell death and tumor regression |
| GB0003224D0 (en) * | 2000-02-11 | 2000-04-05 | Glaxo Group Ltd | Chemical compounds |
| US7235567B2 (en) * | 2000-06-15 | 2007-06-26 | Schering Corporation | Crystalline polymorph of a bisulfate salt of a thrombin receptor antagonist |
| WO2002044166A1 (en) | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
| TW200303742A (en) | 2001-11-21 | 2003-09-16 | Novartis Ag | Organic compounds |
| WO2004064733A2 (en) * | 2003-01-15 | 2004-08-05 | Board Of Regents, University Of Texas System | The use of c-raf inhibitors for the treatment of neurodegenerative diseases |
| EP1831198B1 (en) * | 2004-12-22 | 2009-04-08 | AstraZeneca AB | Pyridine carboxamide derivatives for use as anticancer agents |
| EP1912636B1 (en) * | 2005-07-21 | 2014-06-25 | Ardea Biosciences, Inc. | N-(arylamino)-sulfonamide inhibitors of mek |
| US7842836B2 (en) * | 2006-04-11 | 2010-11-30 | Ardea Biosciences | N-aryl-N'alkyl sulfamides as MEK inhibitors |
| WO2007121481A2 (en) * | 2006-04-18 | 2007-10-25 | Ardea Biosciences, Inc. | Pyridone sulfonamides and pyridone sulfamides as mek inhibitors |
| KR20090111847A (ko) * | 2007-01-19 | 2009-10-27 | 아디아 바이오사이언스즈 인크. | Ｍｅｋ 억제제 |
| WO2008120004A1 (en) * | 2007-04-02 | 2008-10-09 | Astrazeneca Ab | Combination of a mek- inhibitor and a b-raf inhibitor for the treatment of cancer |
-
2008
- 2008-07-28 CA CA2924418A patent/CA2924418A1/en not_active Abandoned
- 2008-07-28 JP JP2010520122A patent/JP5479337B2/ja not_active Expired - Fee Related
- 2008-07-28 EP EP08782470.2A patent/EP2175885B1/en not_active Not-in-force
- 2008-07-28 US US12/671,287 patent/US8648116B2/en not_active Expired - Fee Related
- 2008-07-28 WO PCT/US2008/071397 patent/WO2009018238A1/en not_active Ceased
- 2008-07-28 UA UAA201002026A patent/UA99731C2/ru unknown
- 2008-07-28 CA CA2924436A patent/CA2924436A1/en not_active Abandoned
- 2008-07-28 CA CA2694646A patent/CA2694646C/en not_active Expired - Fee Related
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