JP2000204079A - ジアリ―ルアミン - Google Patents
ジアリ―ルアミンInfo
- Publication number
- JP2000204079A JP2000204079A JP11053551A JP5355199A JP2000204079A JP 2000204079 A JP2000204079 A JP 2000204079A JP 11053551 A JP11053551 A JP 11053551A JP 5355199 A JP5355199 A JP 5355199A JP 2000204079 A JP2000204079 A JP 2000204079A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- phenylamino
- alkyl
- compound
- fluoro
- 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.)
- Withdrawn
Links
- 125000005266 diarylamine group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 28
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 16
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- HGNFTINEEIDDLT-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CN2 HGNFTINEEIDDLT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 206010019280 Heart failures Diseases 0.000 claims abstract description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 4
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 3
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 3
- 201000005202 lung cancer Diseases 0.000 claims abstract description 3
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 3
- -1 (amino Sulfonyl) phenyl Chemical group 0.000 claims description 279
- 239000000203 mixture Substances 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- NTZGEBNJRQSICS-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CO2 NTZGEBNJRQSICS-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- WULDESHELSRYQZ-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-2,1,3-benzothiadiazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NSN=C2C=C1C(O)=O WULDESHELSRYQZ-UHFFFAOYSA-N 0.000 claims description 5
- YKRYPAQULJMUDV-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-2,1,3-benzoxadiazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NON=C2C=C1C(O)=O YKRYPAQULJMUDV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 230000002062 proliferating effect Effects 0.000 claims description 5
- JWAWKFXZGAKZEU-UHFFFAOYSA-N 8-fluoro-7-(4-iodo-2-methylanilino)quinoxaline-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NC=CN=C2C=C1C(O)=O JWAWKFXZGAKZEU-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010040070 Septic Shock Diseases 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- ZXDUEQMOCGOOEX-UHFFFAOYSA-N 1-acetyl-7-fluoro-6-(4-iodo-2-methylanilino)benzimidazole-5-carboxylic acid Chemical compound FC1=C2N(C(=O)C)C=NC2=CC(C(O)=O)=C1NC1=CC=C(I)C=C1C ZXDUEQMOCGOOEX-UHFFFAOYSA-N 0.000 claims description 2
- UXILCSZNSIYGAV-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-7-fluoro-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical compound FC1=C2NC(CCN(C)C)=NC2=CC(C(O)=O)=C1NC1=CC=C(I)C=C1C UXILCSZNSIYGAV-UHFFFAOYSA-N 0.000 claims description 2
- RPZALGIZXFACEO-UHFFFAOYSA-N 7-fluoro-2-(2-hydroxyethyl)-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=C(CCO)N2 RPZALGIZXFACEO-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 2
- 208000006029 Cardiomegaly Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 229940121849 Mitotic inhibitor Drugs 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 210000001185 bone marrow Anatomy 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000002611 ovarian Effects 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 206010010904 Convulsion Diseases 0.000 claims 2
- 125000001288 lysyl group Chemical group 0.000 claims 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- GUOVBFFLXKJFEE-UHFFFAOYSA-N 2h-benzotriazole-5-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NNN=C21 GUOVBFFLXKJFEE-UHFFFAOYSA-N 0.000 claims 1
- 241001024304 Mino Species 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 abstract description 6
- 150000002430 hydrocarbons Chemical class 0.000 abstract description 4
- WEPXLRANFJEOFZ-UHFFFAOYSA-N 2,3,4-trifluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1F WEPXLRANFJEOFZ-UHFFFAOYSA-N 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract description 2
- 230000001684 chronic effect Effects 0.000 abstract 1
- POEUEIJDOLLSQC-UHFFFAOYSA-N methyl 7-fluoro-6-(2-methylanilino)-3h-benzimidazole-5-carboxylate Chemical compound COC(=O)C1=CC=2N=CNC=2C(F)=C1NC1=CC=CC=C1C POEUEIJDOLLSQC-UHFFFAOYSA-N 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 69
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 22
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 108091054455 MAP kinase family Proteins 0.000 description 18
- 102000043136 MAP kinase family Human genes 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000002994 raw material Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000000872 buffer Substances 0.000 description 14
- 239000000499 gel Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 108091000080 Phosphotransferase Proteins 0.000 description 11
- 102000020233 phosphotransferase Human genes 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 230000007017 scission Effects 0.000 description 10
- 238000003828 vacuum filtration Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
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- 150000001408 amides Chemical class 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
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- 238000004519 manufacturing process Methods 0.000 description 7
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 6
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
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- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
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- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 4
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
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- 229940095064 tartrate Drugs 0.000 description 1
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- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
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- CPRPKIMXLHBUGA-UHFFFAOYSA-N triethyltin Chemical group CC[Sn](CC)CC CPRPKIMXLHBUGA-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11587399P | 1999-01-13 | 1999-01-13 | |
| US115873 | 1999-01-13 |
Publications (2)
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| JP2000204079A true JP2000204079A (ja) | 2000-07-25 |
| JP2000204079A5 JP2000204079A5 (enExample) | 2006-04-27 |
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Family Applications (1)
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| JP11053551A Withdrawn JP2000204079A (ja) | 1999-01-13 | 1999-03-02 | ジアリ―ルアミン |
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| ZA (1) | ZA200105224B (enExample) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002534510A (ja) * | 1999-01-13 | 2002-10-15 | ワーナー−ランバート・カンパニー | ベンゾ複素環およびｍｅｋ阻害剤としてのその使用 |
| JP2006528621A (ja) * | 2003-07-24 | 2006-12-21 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | Ｎ−メチル−置換ベンゾアミダゾール |
| JP2010501584A (ja) * | 2006-08-21 | 2010-01-21 | ジェネンテック・インコーポレーテッド | アザベンゾチオフェニル化合物および使用方法 |
| JP2010501585A (ja) * | 2006-08-21 | 2010-01-21 | ジェネンテック・インコーポレーテッド | アザベンゾフラニル化合物および使用方法 |
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| AU2004270699B2 (en) * | 2003-09-03 | 2011-11-10 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
| JP2015503597A (ja) * | 2012-01-17 | 2015-02-02 | ティエンジン ビンジャン ファーマ， インコーポレイテッド | ベンゾ複素環式化合物およびその使用 |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998037881A1 (en) * | 1997-02-28 | 1998-09-03 | Warner Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
-
1999
- 1999-03-02 JP JP11053551A patent/JP2000204079A/ja not_active Withdrawn
-
2001
- 2001-06-25 ZA ZA200105224A patent/ZA200105224B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998037881A1 (en) * | 1997-02-28 | 1998-09-03 | Warner Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002534510A (ja) * | 1999-01-13 | 2002-10-15 | ワーナー−ランバート・カンパニー | ベンゾ複素環およびｍｅｋ阻害剤としてのその使用 |
| JP2006528621A (ja) * | 2003-07-24 | 2006-12-21 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | Ｎ−メチル−置換ベンゾアミダゾール |
| JP4896717B2 (ja) * | 2003-07-24 | 2012-03-14 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | Ｎ−メチル−置換ベンゾアミダゾール |
| AU2004270699B2 (en) * | 2003-09-03 | 2011-11-10 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| JP2010501585A (ja) * | 2006-08-21 | 2010-01-21 | ジェネンテック・インコーポレーテッド | アザベンゾフラニル化合物および使用方法 |
| JP2010501584A (ja) * | 2006-08-21 | 2010-01-21 | ジェネンテック・インコーポレーテッド | アザベンゾチオフェニル化合物および使用方法 |
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| US9084781B2 (en) | 2008-12-10 | 2015-07-21 | Novartis Ag | MEK mutations conferring resistance to MEK inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| US8637246B2 (en) | 2010-02-25 | 2014-01-28 | Dana-Farber Cancer Institute, Inc. | BRAF mutations conferring resistance to BRAF inhibitors |
| US9279144B2 (en) | 2010-02-25 | 2016-03-08 | Dana-Farber Cancer Institute, Inc. | Screening method for BRAF inhibitors |
| EP3028699A1 (en) | 2010-02-25 | 2016-06-08 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| US11078540B2 (en) | 2010-03-09 | 2021-08-03 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
| JP2015503597A (ja) * | 2012-01-17 | 2015-02-02 | ティエンジン ビンジャン ファーマ， インコーポレイテッド | ベンゾ複素環式化合物およびその使用 |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200105224B (en) | 2002-09-25 |
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