CN105980365B - 作为mIDH1抑制剂的苯并咪唑-2-胺 - Google Patents
作为mIDH1抑制剂的苯并咪唑-2-胺 Download PDFInfo
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- CN105980365B CN105980365B CN201580008153.3A CN201580008153A CN105980365B CN 105980365 B CN105980365 B CN 105980365B CN 201580008153 A CN201580008153 A CN 201580008153A CN 105980365 B CN105980365 B CN 105980365B
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- China
- Prior art keywords
- phenyl
- trimethylcyclohexyl
- amino
- trifluoromethoxy
- benzimidazole
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- 239000003112 inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 361
- 238000000034 method Methods 0.000 claims abstract description 77
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 397
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 388
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 271
- -1 C1-C3Alkoxy Chemical group 0.000 claims description 240
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 163
- 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 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 146
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 112
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 108
- 125000005843 halogen group Chemical group 0.000 claims description 105
- 150000003851 azoles Chemical class 0.000 claims description 100
- 239000000203 mixture Substances 0.000 claims description 91
- 125000001424 substituent group Chemical group 0.000 claims description 84
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 83
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 82
- 150000003839 salts Chemical class 0.000 claims description 80
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 65
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 63
- 229910052736 halogen Inorganic materials 0.000 claims description 62
- 125000003545 alkoxy group Chemical group 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 150000003254 radicals Chemical class 0.000 claims description 52
- 150000002367 halogens Chemical class 0.000 claims description 48
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 150000002148 esters Chemical class 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 150000002460 imidazoles Chemical class 0.000 claims description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- HTSABYAWKQAHBT-UHFFFAOYSA-N trans 3-methylcyclohexanol Natural products CC1CCCC(O)C1 HTSABYAWKQAHBT-UHFFFAOYSA-N 0.000 claims description 35
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 29
- 239000000126 substance Substances 0.000 claims description 28
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- NKWCGTOZTHZDHB-UHFFFAOYSA-N 1h-imidazol-1-ium-4-carboxylate Chemical compound OC(=O)C1=CNC=N1 NKWCGTOZTHZDHB-UHFFFAOYSA-N 0.000 claims description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 claims description 13
- 229910021529 ammonia Inorganic materials 0.000 claims description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 claims description 7
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229940043230 sarcosine Drugs 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 150000002430 hydrocarbons Chemical group 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 238000012546 transfer Methods 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000028709 inflammatory response Effects 0.000 claims description 4
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 4
- 230000004083 survival effect Effects 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- 230000010261 cell growth Effects 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 230000002489 hematologic effect Effects 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 238000013507 mapping Methods 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 208000009849 Female Genital Neoplasms Diseases 0.000 claims description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 201000011523 endocrine gland cancer Diseases 0.000 claims description 2
- 230000001900 immune effect Effects 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000037841 lung tumor Diseases 0.000 claims description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
- 208000023958 prostate neoplasm Diseases 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 61
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 22
- 239000004471 Glycine Substances 0.000 claims 11
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 9
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims 9
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 7
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 claims 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 6
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims 6
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 5
- RJZJWNYCLYAWCD-DOTOQJQBSA-N N-[4-(trifluoromethoxy)phenyl]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-2-amine Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC=C2)(F)F RJZJWNYCLYAWCD-DOTOQJQBSA-N 0.000 claims 5
- RJZJWNYCLYAWCD-WBVHZDCISA-N N-[4-(trifluoromethoxy)phenyl]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-2-amine Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC=C2)(F)F RJZJWNYCLYAWCD-WBVHZDCISA-N 0.000 claims 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 4
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 4
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims 4
- XJVCBQQIEWBUJL-UHFFFAOYSA-N 1,1-dioxothiane-4-carboxamide Chemical compound NC(=O)C1CCS(=O)(=O)CC1 XJVCBQQIEWBUJL-UHFFFAOYSA-N 0.000 claims 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 3
- RMPWZOLDNCRJPR-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C=N[CH]1 RMPWZOLDNCRJPR-UHFFFAOYSA-N 0.000 claims 3
- GVETXSQMEGUJHE-HLTSBHQESA-N N-[5-methyl-6-[(1R,5R)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]-4-(trifluoromethoxy)aniline Chemical compound CC1=CC=CC(C1[C@H]1CC(C[C@@H](C1)C)(C)C)NC1=CC=C(C=C1)OC(F)(F)F GVETXSQMEGUJHE-HLTSBHQESA-N 0.000 claims 3
- GVETXSQMEGUJHE-DSSREEIYSA-N N-[5-methyl-6-[(1S,5S)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]-4-(trifluoromethoxy)aniline Chemical compound CC1=CC=CC(C1[C@@H]1CC(C[C@H](C1)C)(C)C)NC1=CC=C(C=C1)OC(F)(F)F GVETXSQMEGUJHE-DSSREEIYSA-N 0.000 claims 3
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 3
- 229940000635 beta-alanine Drugs 0.000 claims 3
- 229940124530 sulfonamide Drugs 0.000 claims 3
- OLHNTPMHCBIKOT-UHFFFAOYSA-N 1-(3,3-dimethylcyclohexyl)-6-methyl-2-(4-propan-2-ylanilino)benzimidazole-5-carboxylic acid Chemical compound CC1(CC(CCC1)N1C(=NC2=C1C=C(C(=C2)C(=O)O)C)NC2=CC=C(C=C2)C(C)C)C OLHNTPMHCBIKOT-UHFFFAOYSA-N 0.000 claims 2
- OLHNTPMHCBIKOT-HXUWFJFHSA-N 1-[(1R)-3,3-dimethylcyclohexyl]-6-methyl-2-(4-propan-2-ylanilino)benzimidazole-5-carboxylic acid Chemical compound CC1(C[C@@H](CCC1)N1C(=NC2=C1C=C(C(=C2)C(=O)O)C)NC1=CC=C(C=C1)C(C)C)C OLHNTPMHCBIKOT-HXUWFJFHSA-N 0.000 claims 2
- OLHNTPMHCBIKOT-FQEVSTJZSA-N 1-[(1S)-3,3-dimethylcyclohexyl]-6-methyl-2-(4-propan-2-ylanilino)benzimidazole-5-carboxylic acid Chemical compound CC1(C[C@H](CCC1)N1C(=NC2=C1C=C(C(=C2)C(=O)O)C)NC2=CC=C(C=C2)C(C)C)C OLHNTPMHCBIKOT-FQEVSTJZSA-N 0.000 claims 2
- RTGDONUAFURLEW-OXJNMPFZSA-N 2-(4-ethylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)O RTGDONUAFURLEW-OXJNMPFZSA-N 0.000 claims 2
- RTGDONUAFURLEW-UZLBHIALSA-N 2-(4-ethylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)O RTGDONUAFURLEW-UZLBHIALSA-N 0.000 claims 2
- ZVCCJDSGFMZHQD-PGRDOPGGSA-N 2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carbonitrile Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C#N ZVCCJDSGFMZHQD-PGRDOPGGSA-N 0.000 claims 2
- GWMNDWCQEWDFPA-LAUBAEHRSA-N 2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)O GWMNDWCQEWDFPA-LAUBAEHRSA-N 0.000 claims 2
- ZVCCJDSGFMZHQD-GCJKJVERSA-N 2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carbonitrile Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C#N ZVCCJDSGFMZHQD-GCJKJVERSA-N 0.000 claims 2
- GWMNDWCQEWDFPA-UTKZUKDTSA-N 2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)O GWMNDWCQEWDFPA-UTKZUKDTSA-N 0.000 claims 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 2
- OMRCXTBFBBWTDL-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=CC(Cl)=C1 OMRCXTBFBBWTDL-UHFFFAOYSA-N 0.000 claims 2
- QHBJNHHECQXYKW-FBIZOPLVSA-N N-[3-methyl-6-[(1R,5R)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]-4-(trifluoromethoxy)aniline Chemical compound CC1=CC(C(C=C1)[C@H]1CC(C[C@@H](C1)C)(C)C)NC1=CC=C(C=C1)OC(F)(F)F QHBJNHHECQXYKW-FBIZOPLVSA-N 0.000 claims 2
- QHBJNHHECQXYKW-AMZMEHNNSA-N N-[3-methyl-6-[(1S,5S)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]-4-(trifluoromethoxy)aniline Chemical compound CC1=CC(C(C=C1)[C@@H]1CC(C[C@H](C1)C)(C)C)NC1=CC=C(C=C1)OC(F)(F)F QHBJNHHECQXYKW-AMZMEHNNSA-N 0.000 claims 2
- SQQGDHGUFJVQLK-FBIZOPLVSA-N N-methyl-4-(trifluoromethoxy)-N-[6-[(1R,5R)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]aniline Chemical compound CN(C1C(C=CC=C1)[C@H]1CC(C[C@@H](C1)C)(C)C)C1=CC=C(C=C1)OC(F)(F)F SQQGDHGUFJVQLK-FBIZOPLVSA-N 0.000 claims 2
- SQQGDHGUFJVQLK-AMZMEHNNSA-N N-methyl-4-(trifluoromethoxy)-N-[6-[(1S,5S)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]aniline Chemical compound CN(C1C(C=CC=C1)[C@@H]1CC(C[C@H](C1)C)(C)C)C1=CC=C(C=C1)OC(F)(F)F SQQGDHGUFJVQLK-AMZMEHNNSA-N 0.000 claims 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 2
- 239000004202 carbamide Substances 0.000 claims 2
- ZTRPYTHOEREHEN-UHFFFAOYSA-N piperazine pyridine Chemical compound N1CCNCC1.N1=CC=CC=C1.N1=CC=CC=C1 ZTRPYTHOEREHEN-UHFFFAOYSA-N 0.000 claims 2
- 208000029584 urinary system neoplasm Diseases 0.000 claims 2
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 1
- JONZGTDAOILKNE-UHFFFAOYSA-N 1-(3,3-dimethylcyclohexyl)-6-methyl-2-[4-(trifluoromethoxy)anilino]benzimidazole-5-carboxylic acid Chemical compound CC1(CC(CCC1)N1C(=NC2=C1C=C(C(=C2)C(=O)O)C)NC2=CC=C(C=C2)OC(F)(F)F)C JONZGTDAOILKNE-UHFFFAOYSA-N 0.000 claims 1
- PZRMEQZKRQWAPK-MAUKXSAKSA-N 2-(3,4,5-trimethoxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound COC=1C=C(C=C(C=1OC)OC)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)O PZRMEQZKRQWAPK-MAUKXSAKSA-N 0.000 claims 1
- PZRMEQZKRQWAPK-QAPCUYQASA-N 2-(3,4,5-trimethoxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound COC=1C=C(C=C(C1OC)OC)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)O PZRMEQZKRQWAPK-QAPCUYQASA-N 0.000 claims 1
- XKUZDGXAHAETPA-HNAYVOBHSA-N 2-(4-cyanoanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(#N)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)O XKUZDGXAHAETPA-HNAYVOBHSA-N 0.000 claims 1
- XKUZDGXAHAETPA-BEFAXECRSA-N 2-(4-cyanoanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound C(#N)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)O XKUZDGXAHAETPA-BEFAXECRSA-N 0.000 claims 1
- LDZOLIBYZLTSOK-KBXCAEBGSA-N 2-(4-fluoroanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylic acid Chemical compound FC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)O LDZOLIBYZLTSOK-KBXCAEBGSA-N 0.000 claims 1
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- LHRRUPLRAORZFG-OXJNMPFZSA-N N-cyclopropyl-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxamide Chemical compound C1(CC1)NC(=O)C1=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=C1 LHRRUPLRAORZFG-OXJNMPFZSA-N 0.000 claims 1
- LHRRUPLRAORZFG-UZLBHIALSA-N N-cyclopropyl-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxamide Chemical compound C1(CC1)NC(=O)C1=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C=C1 LHRRUPLRAORZFG-UZLBHIALSA-N 0.000 claims 1
- TZWCVUSEWQJSRC-NFAVZRQZSA-N N-ethyl-4-(trifluoromethoxy)-N-[6-[(1R,5R)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]aniline Chemical compound C(C)N(C1C(C=CC=C1)[C@H]1CC(C[C@@H](C1)C)(C)C)C1=CC=C(C=C1)OC(F)(F)F TZWCVUSEWQJSRC-NFAVZRQZSA-N 0.000 claims 1
- SQQGDHGUFJVQLK-ZGDXVETISA-N N-methyl-4-(trifluoromethoxy)-N-[6-[(1R,5S)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]aniline Chemical compound CN(C1C(C=CC=C1)[C@H]1CC(C[C@H](C1)C)(C)C)C1=CC=C(C=C1)OC(F)(F)F SQQGDHGUFJVQLK-ZGDXVETISA-N 0.000 claims 1
- SQQGDHGUFJVQLK-UUBYJMPYSA-N N-methyl-4-(trifluoromethoxy)-N-[6-[(1S,5R)-3,3,5-trimethylcyclohexyl]cyclohexa-2,4-dien-1-yl]aniline Chemical compound CN(C1C(C=CC=C1)[C@@H]1CC(C[C@@H](C1)C)(C)C)C1=CC=C(C=C1)OC(F)(F)F SQQGDHGUFJVQLK-UUBYJMPYSA-N 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 claims 1
- KLWYPRNPRNPORS-UHFFFAOYSA-N ethyl 1h-imidazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=CN1 KLWYPRNPRNPORS-UHFFFAOYSA-N 0.000 claims 1
- 230000028993 immune response Effects 0.000 claims 1
- 210000005075 mammary gland Anatomy 0.000 claims 1
- NVPTXHVAPFHALN-QFBILLFUSA-N methyl 2-(3,4,5-trimethoxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound COC=1C=C(C=C(C=1OC)OC)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC NVPTXHVAPFHALN-QFBILLFUSA-N 0.000 claims 1
- NVPTXHVAPFHALN-APWZRJJASA-N methyl 2-(3,4,5-trimethoxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound COC=1C=C(C=C(C1OC)OC)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC NVPTXHVAPFHALN-APWZRJJASA-N 0.000 claims 1
- AXRFMMNYIXZSHM-PGRDOPGGSA-N methyl 2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC AXRFMMNYIXZSHM-PGRDOPGGSA-N 0.000 claims 1
- AXRFMMNYIXZSHM-GCJKJVERSA-N methyl 2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC AXRFMMNYIXZSHM-GCJKJVERSA-N 0.000 claims 1
- GDNBRBZHBZRGCB-GHTZIAJQSA-N methyl 2-(4-propan-2-yloxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC GDNBRBZHBZRGCB-GHTZIAJQSA-N 0.000 claims 1
- GDNBRBZHBZRGCB-NQIIRXRSSA-N methyl 2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC GDNBRBZHBZRGCB-NQIIRXRSSA-N 0.000 claims 1
- SMEVPTYDIWFZOX-PGRDOPGGSA-N methyl 2-(4-tert-butylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC SMEVPTYDIWFZOX-PGRDOPGGSA-N 0.000 claims 1
- SMEVPTYDIWFZOX-GCJKJVERSA-N methyl 2-(4-tert-butylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC SMEVPTYDIWFZOX-GCJKJVERSA-N 0.000 claims 1
- RQGHSWSXRSSPPL-MAUKXSAKSA-N methyl 2-[4-(difluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)F RQGHSWSXRSSPPL-MAUKXSAKSA-N 0.000 claims 1
- RQGHSWSXRSSPPL-QAPCUYQASA-N methyl 2-[4-(difluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)F RQGHSWSXRSSPPL-QAPCUYQASA-N 0.000 claims 1
- QLFOJPVWSNKVMF-DYESRHJHSA-N methyl 2-[4-(dimethylamino)anilino]-1-[(1R,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound CN(C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)C QLFOJPVWSNKVMF-DYESRHJHSA-N 0.000 claims 1
- QLFOJPVWSNKVMF-UWJYYQICSA-N methyl 2-[4-(dimethylamino)anilino]-1-[(1S,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound CN(C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)C QLFOJPVWSNKVMF-UWJYYQICSA-N 0.000 claims 1
- BUONBQRWWDSYIP-MAUKXSAKSA-N methyl 2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F BUONBQRWWDSYIP-MAUKXSAKSA-N 0.000 claims 1
- BUONBQRWWDSYIP-CRAIPNDOSA-N methyl 2-[4-(trifluoromethoxy)anilino]-1-[(1R,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F BUONBQRWWDSYIP-CRAIPNDOSA-N 0.000 claims 1
- BUONBQRWWDSYIP-YJBOKZPZSA-N methyl 2-[4-(trifluoromethoxy)anilino]-1-[(1S,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F BUONBQRWWDSYIP-YJBOKZPZSA-N 0.000 claims 1
- BUONBQRWWDSYIP-QAPCUYQASA-N methyl 2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F BUONBQRWWDSYIP-QAPCUYQASA-N 0.000 claims 1
- LXSQCFMYEYHNFJ-HNAYVOBHSA-N methyl 2-[4-(trifluoromethyl)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F LXSQCFMYEYHNFJ-HNAYVOBHSA-N 0.000 claims 1
- LXSQCFMYEYHNFJ-BEFAXECRSA-N methyl 2-[4-(trifluoromethyl)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)C(=O)OC)(F)F LXSQCFMYEYHNFJ-BEFAXECRSA-N 0.000 claims 1
- MTSNWHXEHAHKFM-DOTOQJQBSA-N methyl 6-(2,2,2-trifluoroethoxy)-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)C(=O)OC)(F)F MTSNWHXEHAHKFM-DOTOQJQBSA-N 0.000 claims 1
- MTSNWHXEHAHKFM-WBVHZDCISA-N methyl 6-(2,2,2-trifluoroethoxy)-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound FC(COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)C(=O)OC)(F)F MTSNWHXEHAHKFM-WBVHZDCISA-N 0.000 claims 1
- RTYBYVPYYMCJDN-GHTZIAJQSA-N methyl 6-methoxy-2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)C(=O)OC RTYBYVPYYMCJDN-GHTZIAJQSA-N 0.000 claims 1
- RTYBYVPYYMCJDN-NQIIRXRSSA-N methyl 6-methoxy-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C=1)C(=O)OC RTYBYVPYYMCJDN-NQIIRXRSSA-N 0.000 claims 1
- UIGQQSQUYBFUFE-PGRDOPGGSA-N methyl 6-methyl-2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=C(C(=C2)C(=O)OC)C UIGQQSQUYBFUFE-PGRDOPGGSA-N 0.000 claims 1
- UIGQQSQUYBFUFE-GCJKJVERSA-N methyl 6-methyl-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=C(C(=C2)C(=O)OC)C UIGQQSQUYBFUFE-GCJKJVERSA-N 0.000 claims 1
- RHDUUZGCENKCTI-HNAYVOBHSA-N methyl 6-methyl-2-[4-(trifluoromethyl)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)C(=O)OC RHDUUZGCENKCTI-HNAYVOBHSA-N 0.000 claims 1
- RHDUUZGCENKCTI-BEFAXECRSA-N methyl 6-methyl-2-[4-(trifluoromethyl)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazole-5-carboxylate Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C=1)C(=O)OC RHDUUZGCENKCTI-BEFAXECRSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
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- FEEWYJLORPPHIP-UHFFFAOYSA-N methyl 2,2-dimethylpropaneperoxoate Chemical compound COOC(=O)C(C)(C)C FEEWYJLORPPHIP-UHFFFAOYSA-N 0.000 description 1
- SDTNYNDUSFXOMP-UHFFFAOYSA-N methyl 3-amino-4-[(3,3,5,5-tetramethylcyclohexyl)amino]benzoate Chemical compound COC(C1=CC(=C(C=C1)NC1CC(CC(C1)(C)C)(C)C)N)=O SDTNYNDUSFXOMP-UHFFFAOYSA-N 0.000 description 1
- MCEBXXSZFFMJLM-UHFFFAOYSA-N methyl 3-amino-4-bromo-2-nitrobenzoate Chemical compound COC(=O)C1=CC=C(Br)C(N)=C1[N+]([O-])=O MCEBXXSZFFMJLM-UHFFFAOYSA-N 0.000 description 1
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- JWLVSMLOEYNNHO-UHFFFAOYSA-N methyl 4-amino-2-methyl-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=C(N)C=C1C JWLVSMLOEYNNHO-UHFFFAOYSA-N 0.000 description 1
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- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
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- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
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- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
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- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
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- 229940044551 receptor antagonist Drugs 0.000 description 1
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- PANBYUAFMMOFOV-UHFFFAOYSA-N sodium;sulfuric acid Chemical compound [Na].OS(O)(=O)=O PANBYUAFMMOFOV-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
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- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000004079 stearyl 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])C([H])([H])C([H])([H])C([H])([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
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- 235000012222 talc Nutrition 0.000 description 1
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- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
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- NONOKGVFTBWRLD-UHFFFAOYSA-N thioisocyanate group Chemical group S(N=C=O)N=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 1
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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- 230000035899 viability Effects 0.000 description 1
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Claims (44)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14154680 | 2014-02-11 | ||
EP14154680.4 | 2014-02-11 | ||
EP14182001.9 | 2014-08-22 | ||
EP14182001 | 2014-08-22 | ||
PCT/EP2015/052675 WO2015121209A1 (en) | 2014-02-11 | 2015-02-10 | Benzimidazol-2-amines as midh1 inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105980365A CN105980365A (zh) | 2016-09-28 |
CN105980365B true CN105980365B (zh) | 2019-06-21 |
Family
ID=52574113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201580008153.3A Expired - Fee Related CN105980365B (zh) | 2014-02-11 | 2015-02-10 | 作为mIDH1抑制剂的苯并咪唑-2-胺 |
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US (1) | US9951027B2 (zh) |
EP (1) | EP3105210B1 (zh) |
JP (1) | JP6688735B2 (zh) |
CN (1) | CN105980365B (zh) |
CA (1) | CA2939021C (zh) |
ES (1) | ES2732902T3 (zh) |
HK (1) | HK1226398A1 (zh) |
WO (1) | WO2015121209A1 (zh) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PE20170143A1 (es) | 2014-02-11 | 2017-03-19 | Bayer Pharma AG | Benzimidazol-2-aminas como inhibidores de midh1 |
US9951027B2 (en) | 2014-02-11 | 2018-04-24 | Bayer Pharma Aktiengesellschaft | Benzimidazol-2-amines as MIDH1 inhibitors |
JP6783756B2 (ja) * | 2014-10-23 | 2020-11-11 | ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ | mIDH1阻害剤としてのベンゾイミダゾール−2−アミン |
EP3209660B1 (en) * | 2014-10-23 | 2020-06-17 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | 1-cyclohexyl-2-phenylaminobenzimidazoles as midh1 inhibitors for the treatment of tumors |
MA41179A (fr) | 2014-12-19 | 2017-10-24 | Cancer Research Tech Ltd | Composés inhibiteurs de parg |
US10370339B2 (en) | 2015-06-08 | 2019-08-06 | Bayer Pharma Aktiengesellschaft | N-Methylbenzimidazoles as mIDH1 inhibitors |
WO2017005674A1 (en) * | 2015-07-07 | 2017-01-12 | Bayer Pharma Aktiengesellschaft | 2-aryl- and 2-arylalkyl-benzimidazoles as midh1 inhibitors |
JP6824954B2 (ja) * | 2015-07-16 | 2021-02-03 | ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ | mIDH1阻害剤としての5−ヒドロキシアルキルベンズイミダゾール |
EP3121166A1 (en) * | 2015-07-21 | 2017-01-25 | Bayer Pharma Aktiengesellschaft | Fused imidazoles as midh1 inhibitors |
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CA2939021A1 (en) | 2015-08-20 |
JP6688735B2 (ja) | 2020-04-28 |
EP3105210B1 (en) | 2019-01-30 |
JP2017505793A (ja) | 2017-02-23 |
CN105980365A (zh) | 2016-09-28 |
WO2015121209A1 (en) | 2015-08-20 |
CA2939021C (en) | 2022-07-12 |
HK1226398A1 (zh) | 2017-09-29 |
EP3105210A1 (en) | 2016-12-21 |
US9951027B2 (en) | 2018-04-24 |
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