HRP20110006T1 - 5-supstituirani-2-fenilaminobenzamidi kao inhibitori mek - Google Patents
5-supstituirani-2-fenilaminobenzamidi kao inhibitori mek Download PDFInfo
- Publication number
- HRP20110006T1 HRP20110006T1 HR20110006T HRP20110006T HRP20110006T1 HR P20110006 T1 HRP20110006 T1 HR P20110006T1 HR 20110006 T HR20110006 T HR 20110006T HR P20110006 T HRP20110006 T HR P20110006T HR P20110006 T1 HRP20110006 T1 HR P20110006T1
- Authority
- HR
- Croatia
- Prior art keywords
- group
- hydroxyethoxy
- difluoro
- benzamide
- methyl
- Prior art date
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- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title claims 2
- 229940054066 benzamide antipsychotics Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 75
- 150000003839 salts Chemical class 0.000 claims abstract 36
- 201000010099 disease Diseases 0.000 claims abstract 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 9
- 230000002062 proliferating effect Effects 0.000 claims abstract 8
- 125000000217 alkyl group Chemical group 0.000 claims 132
- -1 2-methoxyacetyl group Chemical group 0.000 claims 97
- 125000005843 halogen group Chemical group 0.000 claims 67
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 56
- 125000000623 heterocyclic group Chemical group 0.000 claims 51
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 45
- 125000001424 substituent group Chemical group 0.000 claims 44
- 229910003827 NRaRb Inorganic materials 0.000 claims 43
- 230000015572 biosynthetic process Effects 0.000 claims 29
- 238000003786 synthesis reaction Methods 0.000 claims 29
- 125000003545 alkoxy group Chemical group 0.000 claims 28
- 125000001072 heteroaryl group Chemical group 0.000 claims 28
- 125000003342 alkenyl group Chemical group 0.000 claims 26
- 125000000304 alkynyl group Chemical group 0.000 claims 26
- 125000003277 amino group Chemical group 0.000 claims 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 22
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 22
- 125000004043 oxo group Chemical group O=* 0.000 claims 20
- 239000000543 intermediate Substances 0.000 claims 19
- 125000002947 alkylene group Chemical group 0.000 claims 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 13
- 125000006239 protecting group Chemical group 0.000 claims 12
- 229910052731 fluorine Inorganic materials 0.000 claims 11
- 125000001153 fluoro group Chemical group F* 0.000 claims 11
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 8
- 238000000034 method Methods 0.000 claims 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 7
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 7
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 6
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 6
- 229910052740 iodine Inorganic materials 0.000 claims 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 5
- 229910052801 chlorine Inorganic materials 0.000 claims 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims 5
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 5
- 239000013067 intermediate product Substances 0.000 claims 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 5
- 239000004480 active ingredient Substances 0.000 claims 4
- 239000002904 solvent Substances 0.000 claims 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 3
- 208000012659 Joint disease Diseases 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 238000009833 condensation Methods 0.000 claims 3
- 230000005494 condensation Effects 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 3
- 230000007935 neutral effect Effects 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- KRLVJGDCIOMJDA-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-methylsulfinylethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCS(=O)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F KRLVJGDCIOMJDA-UHFFFAOYSA-N 0.000 claims 2
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 2
- 230000001419 dependent effect Effects 0.000 claims 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 201000008482 osteoarthritis Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 230000019491 signal transduction Effects 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 206010046766 uterine cancer Diseases 0.000 claims 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
- DDYPLIKUTQPBKC-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-(2-hydroxyethoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1Cl DDYPLIKUTQPBKC-UHFFFAOYSA-N 0.000 claims 1
- UMFFAUKWGWKOER-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(2-hydroxyethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1Cl UMFFAUKWGWKOER-UHFFFAOYSA-N 0.000 claims 1
- VTTRZTASCOJJLE-UHFFFAOYSA-N 2-(4-ethenyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-(2-hydroxyethoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(C=C)C=C1F VTTRZTASCOJJLE-UHFFFAOYSA-N 0.000 claims 1
- QEYGMBIIDZTWBH-UHFFFAOYSA-N 2-(4-ethenyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(2-hydroxyethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(C=C)C=C1F QEYGMBIIDZTWBH-UHFFFAOYSA-N 0.000 claims 1
- IWUXQVAYFVEXJE-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-(2-hydroxyethoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(C#C)C=C1F IWUXQVAYFVEXJE-UHFFFAOYSA-N 0.000 claims 1
- RTIOIHUIBZFJTH-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(2-hydroxyethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(C#C)C=C1F RTIOIHUIBZFJTH-UHFFFAOYSA-N 0.000 claims 1
- JLOPYTHHDLZIAN-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(2-hydroxyethylsulfonylamino)methyl]benzamide Chemical compound OCCONC(=O)C1=CC(CNS(=O)(=O)CCO)=C(F)C(F)=C1NC1=CC=C(C#C)C=C1F JLOPYTHHDLZIAN-UHFFFAOYSA-N 0.000 claims 1
- YKILMIQZXGUOJZ-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(3-hydroxypropanoylamino)methyl]benzamide Chemical compound OCCONC(=O)C1=CC(CNC(=O)CCO)=C(F)C(F)=C1NC1=CC=C(C#C)C=C1F YKILMIQZXGUOJZ-UHFFFAOYSA-N 0.000 claims 1
- UUVWNZYENDJHMQ-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(3-oxo-1,2-oxazolidin-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(=CC=2)C#C)F)C(C(=O)NOCCO)=CC=1CN1OCCC1=O UUVWNZYENDJHMQ-UHFFFAOYSA-N 0.000 claims 1
- KHYHKBLBDVIBHB-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[(3-oxo-1,4,2-dioxazinan-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(=CC=2)C#C)F)C(C(=O)NOCCO)=CC=1CN1OCCOC1=O KHYHKBLBDVIBHB-UHFFFAOYSA-N 0.000 claims 1
- JYYJRVAAGMELOA-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[[(2-hydroxy-2-methylpropoxy)amino]methyl]benzamide Chemical compound FC1=C(F)C(CNOCC(C)(O)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(C#C)C=C1F JYYJRVAAGMELOA-UHFFFAOYSA-N 0.000 claims 1
- ZMZFAUADMNYXLD-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[[methoxy(2-methylpropanoyl)amino]methyl]benzamide Chemical compound FC1=C(F)C(CN(OC)C(=O)C(C)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(C#C)C=C1F ZMZFAUADMNYXLD-UHFFFAOYSA-N 0.000 claims 1
- RJLQTPYRHSOPEK-UHFFFAOYSA-N 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)-5-[[methoxy(propanoyl)amino]methyl]benzamide Chemical compound FC1=C(F)C(CN(C(=O)CC)OC)=CC(C(=O)NOCCO)=C1NC1=CC=C(C#C)C=C1F RJLQTPYRHSOPEK-UHFFFAOYSA-N 0.000 claims 1
- BLGJHQMNSBYLEZ-UHFFFAOYSA-N 2-hydroxyethanesulfonamide Chemical group NS(=O)(=O)CCO BLGJHQMNSBYLEZ-UHFFFAOYSA-N 0.000 claims 1
- VGRUUSGSHQZWBJ-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[(3-hydroxy-2,2-dimethylpropoxy)methyl]-n-(2-hydroxyethoxy)benzamide Chemical compound FC1=C(F)C(COCC(C)(CO)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F VGRUUSGSHQZWBJ-UHFFFAOYSA-N 0.000 claims 1
- QTXJVCLPGFQMTH-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[[(2-hydroxyacetyl)-methoxyamino]methyl]-n-(2-hydroxyethoxy)benzamide Chemical compound FC1=C(F)C(CN(OC)C(=O)CO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F QTXJVCLPGFQMTH-UHFFFAOYSA-N 0.000 claims 1
- WTUVWJNCLQGTJN-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[[(2-hydroxyacetyl)amino]methyl]-n-(2-hydroxyethoxy)benzamide Chemical compound OCCONC(=O)C1=CC(CNC(=O)CO)=C(F)C(F)=C1NC1=CC=C(I)C=C1F WTUVWJNCLQGTJN-UHFFFAOYSA-N 0.000 claims 1
- XZFVHZABQFLECU-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[[formyl(methoxy)amino]methyl]-n-(2-hydroxyethoxy)benzamide Chemical compound FC1=C(F)C(CN(OC)C=O)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F XZFVHZABQFLECU-UHFFFAOYSA-N 0.000 claims 1
- PVBOBALIHWFPSS-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-(2-hydroxyethoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F PVBOBALIHWFPSS-UHFFFAOYSA-N 0.000 claims 1
- QBKQZWXHOJAMRP-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-(2-methylsulfonylethoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCS(=O)(=O)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F QBKQZWXHOJAMRP-UHFFFAOYSA-N 0.000 claims 1
- FPHDATNPPRVROU-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-(2-morpholin-4-ylethoxymethyl)benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1COCCN1CCOCC1 FPHDATNPPRVROU-UHFFFAOYSA-N 0.000 claims 1
- LIYQSSHOHBHGFX-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-(3-hydroxypropoxymethyl)benzamide Chemical compound FC1=C(F)C(COCCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F LIYQSSHOHBHGFX-UHFFFAOYSA-N 0.000 claims 1
- BNQFXDJDHXHATK-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(1-hydroxy-2-methylpropan-2-yl)oxymethyl]benzamide Chemical compound FC1=C(F)C(COC(C)(CO)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F BNQFXDJDHXHATK-UHFFFAOYSA-N 0.000 claims 1
- DJOJPILWCZHRPY-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-hydroxyethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F DJOJPILWCZHRPY-UHFFFAOYSA-N 0.000 claims 1
- CSWOCZQPALZHRD-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-hydroxyethylsulfonylamino)methyl]benzamide Chemical compound OCCONC(=O)C1=CC(CNS(=O)(=O)CCO)=C(F)C(F)=C1NC1=CC=C(I)C=C1F CSWOCZQPALZHRD-UHFFFAOYSA-N 0.000 claims 1
- MKWAVLAGRZELNQ-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-methylsulfonylethoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCS(=O)(=O)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F MKWAVLAGRZELNQ-UHFFFAOYSA-N 0.000 claims 1
- ROOBEQDCKQYMPD-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-oxo-1,3-diazinan-1-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1CCCNC1=O ROOBEQDCKQYMPD-UHFFFAOYSA-N 0.000 claims 1
- XYCVVPRSQFHGMW-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-oxo-1,3-oxazolidin-3-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1CCOC1=O XYCVVPRSQFHGMW-UHFFFAOYSA-N 0.000 claims 1
- FMSSFLTXZKUJMB-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-oxopiperidin-1-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1CCCCC1=O FMSSFLTXZKUJMB-UHFFFAOYSA-N 0.000 claims 1
- JZOWPVCCPGKWFQ-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(2-oxopyrrolidin-1-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1CCCC1=O JZOWPVCCPGKWFQ-UHFFFAOYSA-N 0.000 claims 1
- IPXSRFLULFHGQF-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-hydroxypropanoylamino)methyl]benzamide Chemical compound OCCONC(=O)C1=CC(CNC(=O)CCO)=C(F)C(F)=C1NC1=CC=C(I)C=C1F IPXSRFLULFHGQF-UHFFFAOYSA-N 0.000 claims 1
- LMKDAMCBWRWHIT-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-hydroxypropoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCCO)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F LMKDAMCBWRWHIT-UHFFFAOYSA-N 0.000 claims 1
- WBIODLIVLLITOU-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-methylsulfanylpropoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCCSC)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F WBIODLIVLLITOU-UHFFFAOYSA-N 0.000 claims 1
- NZFDEAUUMDJFNV-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-methylsulfinylpropoxyamino)methyl]benzamide Chemical compound FC1=C(F)C(CNOCCCS(=O)C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F NZFDEAUUMDJFNV-UHFFFAOYSA-N 0.000 claims 1
- YFALDKOPSLRMJM-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-oxo-1,2-oxazolidin-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1OCCC1=O YFALDKOPSLRMJM-UHFFFAOYSA-N 0.000 claims 1
- AVGMZZMVFXLTSU-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-oxo-1,4,2-dioxazinan-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1OCCOC1=O AVGMZZMVFXLTSU-UHFFFAOYSA-N 0.000 claims 1
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- GLMORDLHKNPTOT-UHFFFAOYSA-N n-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-5-[(3-oxo-1,2-oxazolidin-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCC(O)CO)=CC=1CN1OCCC1=O GLMORDLHKNPTOT-UHFFFAOYSA-N 0.000 claims 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 1
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- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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PCT/JP2005/013620 WO2006011466A1 (ja) | 2004-07-26 | 2005-07-26 | Mek阻害物質としての5-置換-2-フェニルアミノ-ベンズアミド類 |
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HR20110006T HRP20110006T1 (hr) | 2004-07-26 | 2011-01-05 | 5-supstituirani-2-fenilaminobenzamidi kao inhibitori mek |
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EP (1) | EP1780197B9 (xx) |
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TW200520745A (en) | 2003-09-19 | 2005-07-01 | Chugai Pharmaceutical Co Ltd | Novel 4-phenylamino-benzaldoxime derivatives and uses thereof as mitogen-activated protein kinase kinase (MEK) inhibitors |
TWI361066B (en) | 2004-07-26 | 2012-04-01 | Chugai Pharmaceutical Co Ltd | 5-substituted-2-phenylamino benzamides as mek inhibitors |
CN109053523B (zh) | 2005-10-07 | 2022-03-25 | 埃克塞利希斯股份有限公司 | 作为用于治疗增生性疾病的mek抑制剂的吖丁啶 |
AU2007334402B2 (en) | 2006-12-14 | 2014-02-13 | Exelixis, Inc. | Methods of using MEK inhibitors |
JP5651125B2 (ja) | 2008-12-10 | 2015-01-07 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | Mek阻害剤に対する耐性を付与するmek突然変異 |
EP2488507B1 (en) | 2009-10-13 | 2014-12-17 | Allostem Therapeutics LLC | Novel mek inhibitors, useful in the treatment of diseases |
US8637246B2 (en) | 2010-02-25 | 2014-01-28 | Dana-Farber Cancer Institute, Inc. | BRAF mutations conferring resistance to BRAF inhibitors |
ES2714875T3 (es) | 2010-03-09 | 2019-05-30 | Dana Farber Cancer Inst Inc | Métodos de diagnóstico y tratamiento del cáncer en pacientes que presentan o desarrollan resistencia a una primera terapia del cáncer |
WO2012018638A2 (en) | 2010-07-26 | 2012-02-09 | Biomatrica, Inc. | Compositions for stabilizing dna, rna and proteins in blood and other biological samples during shipping and storage at ambient temperatures |
CA2806734A1 (en) | 2010-07-26 | 2012-02-09 | Biomatrica, Inc. | Compositions for stabilizing dna, rna and proteins in saliva and other biological samples during shipping and storage at ambient temperatures |
CA2807510A1 (en) * | 2010-08-05 | 2012-02-09 | Case Western Reserve University | Inhibitors of erk for developmental disorders of neuronal connectivity |
US20130123255A1 (en) * | 2011-11-10 | 2013-05-16 | Chugai Seiyaku Kabushiki Kaisha | Combination of a pi3k inhibitor and a mek inhibitor |
GB201201332D0 (en) | 2012-01-26 | 2012-03-14 | Imp Innovations Ltd | Method |
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 |
CR20200237A (es) | 2012-10-12 | 2020-07-26 | Exelixis Inc | Proceso novedoso para la elaboración de compuestos para su uso en el tratamiento del cáncer (diviisional 2015-0245) |
JP2016034900A (ja) * | 2012-11-26 | 2016-03-17 | 中外製薬株式会社 | 5−置換−2−フェニルアミノ−ベンズアミド類の製造方法 |
JP2016034901A (ja) * | 2012-11-26 | 2016-03-17 | 中外製薬株式会社 | 3,4−ジフルオロ−2−(2−フルオロ−4−ヨード−フェニルアミノ)−n−(2−ヒドロキシ−エトキシ)−5−(3−オキソ−[1,2]オキサジナン−2−イルメチル)−ベンズアミドの新規結晶形 |
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