ZA200105224B - Benzoheterocycles and their use as MEK inhibitors. - Google Patents
Benzoheterocycles and their use as MEK inhibitors. Download PDFInfo
- Publication number
- ZA200105224B ZA200105224B ZA200105224A ZA200105224A ZA200105224B ZA 200105224 B ZA200105224 B ZA 200105224B ZA 200105224 A ZA200105224 A ZA 200105224A ZA 200105224 A ZA200105224 A ZA 200105224A ZA 200105224 B ZA200105224 B ZA 200105224B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- composition
- substance
- alkyl
- treating
- Prior art date
Links
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 87
- -1 heterocyclic radical Chemical class 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 49
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000003342 alkenyl group Chemical group 0.000 claims description 35
- 125000000304 alkynyl group Chemical group 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 15
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 238000002512 chemotherapy Methods 0.000 claims description 7
- 230000002062 proliferating effect Effects 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 208000037803 restenosis Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 3
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 208000006029 Cardiomegaly Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010019842 Hepatomegaly Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 206010040070 Septic Shock Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 229960003668 docetaxel Drugs 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- 229960002066 vinorelbine Drugs 0.000 claims description 3
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 3
- 230000009385 viral infection Effects 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 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
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
- 210000001185 bone marrow Anatomy 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- 229960000922 vinflunine Drugs 0.000 claims description 2
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 55
- 239000003814 drug Substances 0.000 claims 17
- 238000004519 manufacturing process Methods 0.000 claims 16
- 229940121849 Mitotic inhibitor Drugs 0.000 claims 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 4
- 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 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 16
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 16
- 108091054455 MAP kinase family Proteins 0.000 description 11
- 102000043136 MAP kinase family Human genes 0.000 description 11
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 8
- 102000016914 ras Proteins Human genes 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 5
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 5
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 5
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 238000007257 deesterification reaction Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- YHNRUSMOYCDMJS-UHFFFAOYSA-N o-(cyclopropylmethyl)hydroxylamine Chemical compound NOCC1CC1 YHNRUSMOYCDMJS-UHFFFAOYSA-N 0.000 description 5
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 4
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000002083 iodinating effect Effects 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 229940124647 MEK inhibitor Drugs 0.000 description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 125000005027 hydroxyaryl group Chemical group 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- JXDCOWYQTPFFDW-UHFFFAOYSA-N 3-cyclopropyl-7-(4-iodo-2-methylanilino)benzimidazole-4,6-dicarboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(C(O)=O)C=C(C(O)=O)C2=C1N=CN2C1CC1 JXDCOWYQTPFFDW-UHFFFAOYSA-N 0.000 description 2
- XPOWESJOUQPAFB-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-1,3-benzothiazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1SC=N2 XPOWESJOUQPAFB-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 2
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000005001 aminoaryl group Chemical group 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000005020 hydroxyalkenyl group Chemical group 0.000 description 2
- 125000005016 hydroxyalkynyl group Chemical group 0.000 description 2
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000034285 signal transducing proteins Human genes 0.000 description 2
- 108091006024 signal transducing proteins Proteins 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- KSAXEEXZWFPXDR-UHFFFAOYSA-N 2-[1-fluoro-6-(4-iodo-2-methylanilino)benzimidazol-2-yl]ethanol Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(N=C(CCO)N2F)C2=C1 KSAXEEXZWFPXDR-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- GGNAJNQJURDBJL-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-7-fluoro-n-hydroxy-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxamide Chemical compound FC1=C2NC(CCN(C)C)=NC2=CC(C(=O)NO)=C1NC1=CC=C(I)C=C1C GGNAJNQJURDBJL-UHFFFAOYSA-N 0.000 description 1
- SFXAYIOKYDQWQZ-UHFFFAOYSA-N 2-fluoro-6-(4-iodo-2-methylanilino)-1,3-benzothiazole-5-carboxylic acid Chemical compound FC=1SC2=C(N1)C=C(C(=C2)NC2=C(C=C(C=C2)I)C)C(=O)O SFXAYIOKYDQWQZ-UHFFFAOYSA-N 0.000 description 1
- NLXQGGJGIAGXGS-UHFFFAOYSA-N 2-fluoro-N-hydroxy-6-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxamide Chemical compound ONC(=O)C=1C(=CC2=C(N=C(O2)F)C1)NC1=C(C=C(C=C1)I)C NLXQGGJGIAGXGS-UHFFFAOYSA-N 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- COYPLDIXZODDDL-UHFFFAOYSA-N 3h-benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N=CNC2=C1 COYPLDIXZODDDL-UHFFFAOYSA-N 0.000 description 1
- GVJGFOKOTYUZIG-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-1,3-benzoxazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1OC=N2 GVJGFOKOTYUZIG-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- HRWKMQGWQNBQEU-UHFFFAOYSA-N 4-fluoro-n-hydroxy-5-(4-iodo-2-methylanilino)-1,3-benzoxazole-6-carboxamide Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(=O)NO)=C(F)C2=C1OC=N2 HRWKMQGWQNBQEU-UHFFFAOYSA-N 0.000 description 1
- QLCOAHUBGSSUSU-UHFFFAOYSA-N 5-(2-chloro-4-iodoanilino)-6,7-difluoro-3h-benzimidazole-4-carboxylic acid Chemical compound FC1=C(F)C=2N=CNC=2C(C(=O)O)=C1NC1=CC=C(I)C=C1Cl QLCOAHUBGSSUSU-UHFFFAOYSA-N 0.000 description 1
- RLWSRUPYXWPOGY-UHFFFAOYSA-N 5-(2-chloro-4-iodoanilino)-6,7-difluoro-n-hydroxy-3h-benzimidazole-4-carboxamide Chemical compound FC1=C(F)C=2N=CNC=2C(C(=O)NO)=C1NC1=CC=C(I)C=C1Cl RLWSRUPYXWPOGY-UHFFFAOYSA-N 0.000 description 1
- KNNOQDHUFKJNQO-UHFFFAOYSA-N 5-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-6,7-difluoro-3h-benzimidazole-4-carboxamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC=1C(F)=C(F)C=2N=CNC=2C=1C(=O)NOCC1CC1 KNNOQDHUFKJNQO-UHFFFAOYSA-N 0.000 description 1
- MQQUUMCHSMPRDO-UHFFFAOYSA-N 6,7-difluoro-5-(4-iodo-2-methylanilino)-1,3-benzothiazole-4-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(SC=N2)C2=C1C(O)=O MQQUUMCHSMPRDO-UHFFFAOYSA-N 0.000 description 1
- CRKFETQUXJPUIS-UHFFFAOYSA-N 6,7-difluoro-n-hydroxy-2-(2-hydroxyethyl)-5-(4-iodo-2-methylanilino)-3h-benzimidazole-4-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(N=C(CCO)N2)C2=C1C(=O)NO CRKFETQUXJPUIS-UHFFFAOYSA-N 0.000 description 1
- ZSUWOEGIQOMKTB-UHFFFAOYSA-N 6,7-difluoro-n-hydroxy-5-(4-iodo-2-methylanilino)-1,3-benzothiazole-4-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(SC=N2)C2=C1C(=O)NO ZSUWOEGIQOMKTB-UHFFFAOYSA-N 0.000 description 1
- SWGOSOSLNHXNEI-UHFFFAOYSA-N 6,7-difluoro-n-hydroxy-5-(4-iodo-2-methylanilino)-1,3-benzoxazole-4-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(OC=N2)C2=C1C(=O)NO SWGOSOSLNHXNEI-UHFFFAOYSA-N 0.000 description 1
- VTWNARSWAFMSHR-UHFFFAOYSA-N 7,8-difluoro-6-(4-iodo-2-methylanilino)quinoxaline-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(N=CC=N2)C2=C1C(O)=O VTWNARSWAFMSHR-UHFFFAOYSA-N 0.000 description 1
- IBUFXISIDAZACU-UHFFFAOYSA-N 7-(2-chloro-4-iodoanilino)-4-fluoro-n-hydroxy-1,3-benzothiazole-6-carboxamide Chemical compound ONC(=O)C1=CC(F)=C2N=CSC2=C1NC1=CC=C(I)C=C1Cl IBUFXISIDAZACU-UHFFFAOYSA-N 0.000 description 1
- WSQJYEFYHSMTEM-UHFFFAOYSA-N 7-(2-chloro-4-iodoanilino)-n-(cyclopropylmethoxy)-4-fluoro-1,3-benzothiazole-6-carboxamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC=1C=2SC=NC=2C(F)=CC=1C(=O)NOCC1CC1 WSQJYEFYHSMTEM-UHFFFAOYSA-N 0.000 description 1
- CHTNFLXQKGCITA-UHFFFAOYSA-N 7-bromo-4-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(C(O)=O)C=C(Br)C2=C1N=CO2 CHTNFLXQKGCITA-UHFFFAOYSA-N 0.000 description 1
- XVMXZYYIJTURKQ-UHFFFAOYSA-N 7-bromo-n-(cyclopropylmethoxy)-4-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(C(=O)NOCC2CC2)C=C(Br)C2=C1N=CO2 XVMXZYYIJTURKQ-UHFFFAOYSA-N 0.000 description 1
- LSUCQCWJKANBNO-UHFFFAOYSA-N 7-bromo-n-hydroxy-4-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(C(=O)NO)C=C(Br)C2=C1N=CO2 LSUCQCWJKANBNO-UHFFFAOYSA-N 0.000 description 1
- JENDHVLUGWDXEE-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-1,3-benzothiazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CS2 JENDHVLUGWDXEE-UHFFFAOYSA-N 0.000 description 1
- GFCWICPCSIPKGG-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-2h-benzotriazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=NN2 GFCWICPCSIPKGG-UHFFFAOYSA-N 0.000 description 1
- QLTAGCASWONOIQ-UHFFFAOYSA-N 7-fluoro-n-hydroxy-6-(4-iodo-2-methylanilino)-1,3-benzothiazole-5-carboxamide Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(=O)NO)=C(F)C2=C1N=CS2 QLTAGCASWONOIQ-UHFFFAOYSA-N 0.000 description 1
- SBOPTAZFVXWFQR-UHFFFAOYSA-N 7-fluoro-n-hydroxy-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxamide Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(=O)NO)=C(F)C2=C1N=CN2 SBOPTAZFVXWFQR-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 102100023275 Dual specificity mitogen-activated protein kinase kinase 3 Human genes 0.000 description 1
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 1
- 108030004793 Dual-specificity kinases Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101001115394 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 3 Proteins 0.000 description 1
- 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 230000005723 MEK inhibition Effects 0.000 description 1
- ATSUGADWXVJGTA-UHFFFAOYSA-N N-hydroxyquinoxaline-5-carboxamide Chemical compound N1=CC=NC2=CC=CC(=C12)C(=O)NO ATSUGADWXVJGTA-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 102000014750 Phosphorylase Kinase Human genes 0.000 description 1
- 108010064071 Phosphorylase Kinase Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005741 alkyl alkenyl group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005021 aminoalkenyl group Chemical group 0.000 description 1
- 125000005014 aminoalkynyl group Chemical group 0.000 description 1
- 125000005124 aminocycloalkyl group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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
- 230000009849 deactivation Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000003106 haloaryl group Chemical group 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- LTWZLVLRHXHGSM-UHFFFAOYSA-N n-(cyclopropylmethoxy)-4-fluoro-5-(4-iodo-2-methylanilino)-2,1,3-benzoxadiazole-6-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NON=C2C=C1C(=O)NOCC1CC1 LTWZLVLRHXHGSM-UHFFFAOYSA-N 0.000 description 1
- ZLIGVZPPNKVUKF-UHFFFAOYSA-N n-(cyclopropylmethoxy)-7,8-difluoro-6-(4-iodo-2-methylanilino)quinoxaline-5-carboxamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(N=CC=N2)C2=C1C(=O)NOCC1CC1 ZLIGVZPPNKVUKF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000002098 pyridazinyl 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
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 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
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl 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
- 230000009466 transformation Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole 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)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11587399P | 1999-01-13 | 1999-01-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200105224B true ZA200105224B (en) | 2002-09-25 |
Family
ID=22363895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200105224A ZA200105224B (en) | 1999-01-13 | 2001-06-25 | Benzoheterocycles and their use as MEK inhibitors. |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2000204079A (enExample) |
| ZA (1) | ZA200105224B (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL144214A0 (en) * | 1999-01-13 | 2002-05-23 | Warner Lambert Co | Benzoheterocycles and their use as mek inhibitors |
| WO2005009975A2 (en) * | 2003-07-24 | 2005-02-03 | Warner-Lambert Company Llc | Benzimidazole derivatives as mek inhibitors |
| US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| WO2008024725A1 (en) * | 2006-08-21 | 2008-02-28 | Genentech, Inc. | Aza-benzofuranyl compounds and methods of use |
| CA2660963A1 (en) * | 2006-08-21 | 2008-02-28 | Genentech, Inc. | Aza-benzothiophenyl compounds and methods of use |
| CN103204827B (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噻二唑化合物及其制备方法和用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5610398A (en) * | 1997-02-28 | 1998-09-18 | 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
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
|---|---|
| JP2000204079A (ja) | 2000-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200105224B (en) | Benzoheterocycles and their use as MEK inhibitors. | |
| Taha et al. | Novel thiosemicarbazide–oxadiazole hybrids as unprecedented inhibitors of yeast α-glucosidase and in silico binding analysis | |
| AU6058099A (en) | Arylsulfonanilide ureas | |
| Sheppard et al. | Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding | |
| Eldehna et al. | Identification of 3-(piperazinylmethyl) benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights | |
| Hu et al. | Enantioselective [1, 2]-Stevens rearrangement of thiosulfonates to construct dithio-substituted quaternary carbon centers | |
| Filimonov et al. | Water/Alkali-catalyzed reactions of azides with 2-cyanothioacetamides. eco-friendly synthesis of monocyclic and bicyclic 1, 2, 3-thiadiazole-4-carbimidamides and 5-amino-1, 2, 3-triazole-4-carbothioamides | |
| Yousaf et al. | Recent synthetic approaches towards biologically potent derivatives/analogues of theophylline | |
| Bukhari | Synthesis and evaluation of new chalcones and oximes as anticancer agents | |
| You et al. | Enantioselective synthesis of isoquinoline-1, 3 (2 H, 4 H)-dione derivatives via a chiral phosphoric acid catalyzed aza-Friedel–Crafts reaction | |
| Shah et al. | Novel purine derivatives as selective CDK2 inhibitors with potential anticancer activities: design, synthesis and biological evaluation | |
| Sharma et al. | Design and synthesis of thiazole scaffold-based small molecules as anticancer agents targeting the human lactate dehydrogenase a enzyme | |
| Moi et al. | Appliance of the piperidinyl-hydrazidoureido linker to benzenesulfonamide compounds: Synthesis, in vitro and in silico evaluation of potent carbonic anhydrase II, IX and XII inhibitors | |
| Wang et al. | Amidation–Ketonization–Selenation of Terminal Alkynes Using TEMPO and Elemental Selenium | |
| Kumar et al. | Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium | |
| US3560501A (en) | Process for making dihydroquinazolines | |
| Qi et al. | Regio-and stereoselective thiocyanatothiolation of alkynes and alkenes by using NH 4 SCN and N-thiosuccinimides | |
| Esam et al. | Green synthesis, anti-proliferative evaluation, docking, and MD simulations studies of novel 2-piperazinyl quinoxaline derivatives using hercynite sulfaguanidine-SA as a highly efficient and reusable nanocatalyst | |
| Sheikhi-Mohammareh et al. | New efficient design and synthesis of novel antioxidant and antifungal 7-imino [1, 3] selenazolo [4, 5-d] pyrimidine-5 (4 H)-thiones utilizing a base-promoted cascade addition/cyclization sequence | |
| ZA200105219B (en) | 1-Heterocycle substituted diarylamines. | |
| Hassan et al. | Stereoselective synthesis of 2-(2, 4-dinitrophenyl) hydrazono-and (2-tosylhydrazono)-4-oxo-thiazolidine derivatives and screening of their anticancer activity | |
| Chan et al. | Open-chain thiamine analogues as potent inhibitors of thiamine pyrophosphate (TPP)-dependent enzymes | |
| Banoglu et al. | A Series of Thiadiazolyl‐Benzenesulfonamides Incorporating an Aromatic Tail as Isoform‐Selective, Potent Carbonic Anhydrase II/XII Inhibitors | |
| Azam et al. | Identification of 5-amino-1, 3, 4-thiadiazole appended isatins as bioactive small molecules with polypharmacological activities | |
| Maji et al. | Synthesis and antiproliferative potency of 1, 3, 4-thiadiazole and 1, 3-thiazolidine-4-one based new binary heterocyclic molecules: in vitro cell-based anticancer studies |