JP2018511587A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018511587A5 JP2018511587A5 JP2017548261A JP2017548261A JP2018511587A5 JP 2018511587 A5 JP2018511587 A5 JP 2018511587A5 JP 2017548261 A JP2017548261 A JP 2017548261A JP 2017548261 A JP2017548261 A JP 2017548261A JP 2018511587 A5 JP2018511587 A5 JP 2018511587A5
- Authority
- JP
- Japan
- Prior art keywords
- indol
- fluoro
- methyl
- dioxide
- dihydrobenzo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 (-)-Methyl Chemical group 0.000 claims 130
- 229910052736 halogen Inorganic materials 0.000 claims 14
- 150000002367 halogens Chemical class 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 12
- 239000012453 solvate Substances 0.000 claims 11
- 150000001875 compounds Chemical class 0.000 claims 10
- 125000004043 oxo group Chemical group O=* 0.000 claims 10
- 125000000217 alkyl group Chemical group 0.000 claims 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- 125000001424 substituent group Chemical group 0.000 claims 8
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 6
- 125000000623 heterocyclic group Chemical group 0.000 claims 6
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 5
- CJMWCVHRDNPWIE-UHFFFAOYSA-N 3-[5-(6-fluoro-1H-indol-3-yl)-3-(hydroxymethyl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]propane-1,2-diol Chemical compound OC(CN1S(C2=C(C1CO)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O)CO CJMWCVHRDNPWIE-UHFFFAOYSA-N 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- YTBRDCJCTHUZLT-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(2-methylsulfinylethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCS(=O)C)C)C=1 YTBRDCJCTHUZLT-UHFFFAOYSA-N 0.000 claims 3
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 3
- VEVPOVSPCMGGON-SBXXRYSUSA-N (2R)-3-[5-(6-fluoro-1H-indol-3-yl)-3-methyl-1,1-dioxo-3H-1,2-benzothiazol-2-yl]propane-1,2-diol Chemical compound O[C@H](CN1S(C2=C(C1C)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O)CO VEVPOVSPCMGGON-SBXXRYSUSA-N 0.000 claims 2
- VEVPOVSPCMGGON-IAXJKZSUSA-N (2S)-3-[5-(6-fluoro-1H-indol-3-yl)-3-methyl-1,1-dioxo-3H-1,2-benzothiazol-2-yl]propane-1,2-diol Chemical compound O[C@@H](CN1S(C2=C(C1C)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O)CO VEVPOVSPCMGGON-IAXJKZSUSA-N 0.000 claims 2
- IXSJHACANDXCDX-UHFFFAOYSA-N 1-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazol-3-yl]-N,N-dimethylmethanamine Chemical compound CN(C)CC1NS(=O)(=O)C2=C1C=C(C=C2)C1=CNC2=CC(F)=CC=C12 IXSJHACANDXCDX-UHFFFAOYSA-N 0.000 claims 2
- KFMKCVDVXIMKLQ-UHFFFAOYSA-N 1-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazol-3-yl]-N-methylmethanamine Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)CNC)C=1 KFMKCVDVXIMKLQ-UHFFFAOYSA-N 0.000 claims 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- OVOIQZIQNPJJQN-UHFFFAOYSA-N 2-(azetidin-3-yl)-5-(6-fluoro-1H-indol-3-yl)-3-methyl-3H-1,2-benzothiazole 1,1-dioxide Chemical compound N1CC(C1)N1S(C2=C(C1C)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O OVOIQZIQNPJJQN-UHFFFAOYSA-N 0.000 claims 2
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims 2
- KKBGUNRNQNHDIB-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazol-3-yl]ethanol Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)CCO)C=1 KKBGUNRNQNHDIB-UHFFFAOYSA-N 0.000 claims 2
- PPXQYVWTQJWWQN-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-3-(hydroxymethyl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]ethanol Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCO)CO)C=1 PPXQYVWTQJWWQN-UHFFFAOYSA-N 0.000 claims 2
- INNZJFMCCWHXDL-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-3-methyl-1,1-dioxo-3H-1,2-benzothiazol-2-yl]ethanol Chemical compound CC1N(CCO)S(=O)(=O)C2=C1C=C(C=C2)C1=CNC2=CC(F)=CC=C12 INNZJFMCCWHXDL-UHFFFAOYSA-N 0.000 claims 2
- AVRSXTDANSQCNG-UHFFFAOYSA-N 3-cyclopropyl-5-(6-fluoro-1H-indol-3-yl)-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound C1(CC1)C1NS(C2=C1C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O AVRSXTDANSQCNG-UHFFFAOYSA-N 0.000 claims 2
- UDMPUXUCELVCTO-UHFFFAOYSA-N 3-ethyl-5-(6-fluoro-1H-indol-3-yl)-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound C(C)C1NS(C2=C1C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O UDMPUXUCELVCTO-UHFFFAOYSA-N 0.000 claims 2
- BHSNBOZVMIRRMP-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazole-3-carboxamide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)C(=O)N)C=1 BHSNBOZVMIRRMP-UHFFFAOYSA-N 0.000 claims 2
- ZMCRNPLKPSLLOS-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)C)C=1 ZMCRNPLKPSLLOS-UHFFFAOYSA-N 0.000 claims 2
- WGMSRXJXUFKLJT-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(2-methylsulfonylethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCS(=O)(=O)C)C)C=1 WGMSRXJXUFKLJT-UHFFFAOYSA-N 0.000 claims 2
- AKNKCTPWZVPPOD-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(2-morpholin-4-ylethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCN2CCOCC2)C)C=1 AKNKCTPWZVPPOD-UHFFFAOYSA-N 0.000 claims 2
- IANSEGCGGREKGE-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(piperidin-4-ylmethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CC2CCNCC2)C)C=1 IANSEGCGGREKGE-UHFFFAOYSA-N 0.000 claims 2
- YZDVOQUALAJWPU-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-[(1-methyl-1,2,4-triazol-3-yl)methyl]-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CC2=NN(C=N2)C)C)C=1 YZDVOQUALAJWPU-UHFFFAOYSA-N 0.000 claims 2
- DUVOUPARCSJAMO-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-piperidin-4-yl-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)C2CCNCC2)C)C=1 DUVOUPARCSJAMO-UHFFFAOYSA-N 0.000 claims 2
- RMVZJAAFRKPMCT-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-propan-2-yl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)C(C)C)C=1 RMVZJAAFRKPMCT-UHFFFAOYSA-N 0.000 claims 2
- VVVMDJMOERMJPW-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-propyl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)CCC)C=1 VVVMDJMOERMJPW-UHFFFAOYSA-N 0.000 claims 2
- SCRMJNXZQNDGNI-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-N-methyl-1,1-dioxo-2,3-dihydro-1,2-benzothiazole-3-carboxamide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)C(=O)NC)C=1 SCRMJNXZQNDGNI-UHFFFAOYSA-N 0.000 claims 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 2
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- ZWVBNIKEVVRPBQ-UHFFFAOYSA-N [5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazol-3-yl]methanamine Chemical compound NCC1NS(C2=C1C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O ZWVBNIKEVVRPBQ-UHFFFAOYSA-N 0.000 claims 2
- MUYZCDJFMYXXLU-UHFFFAOYSA-N [5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazol-3-yl]methanol Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)CO)C=1 MUYZCDJFMYXXLU-UHFFFAOYSA-N 0.000 claims 2
- PSSSKDUJDVBKPP-UHFFFAOYSA-N [5-(6-fluoro-1H-indol-3-yl)-2-[(1-methyl-1,2,4-triazol-3-yl)methyl]-1,1-dioxo-3H-1,2-benzothiazol-3-yl]methanol Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CC2=NN(C=N2)C)CO)C=1 PSSSKDUJDVBKPP-UHFFFAOYSA-N 0.000 claims 2
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 2
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 2
- BRYVWWIWOBEVKY-AWEZNQCLSA-N (2S)-3-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]propane-1,2-diol Chemical compound O[C@@H](CN1S(C2=C(C1)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O)CO BRYVWWIWOBEVKY-AWEZNQCLSA-N 0.000 claims 1
- YNVGNSUTDNJJNH-CQSZACIVSA-N (3R)-5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(pyridin-2-ylmethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C([C@H](N(S2(=O)=O)CC2=NC=CC=C2)C)C=1 YNVGNSUTDNJJNH-CQSZACIVSA-N 0.000 claims 1
- GZACIBROAWWMDJ-OAHLLOKOSA-N (3R)-5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-[(6-methylpyridin-2-yl)methyl]-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C([C@H](N(S2(=O)=O)CC2=NC(=CC=C2)C)C)C=1 GZACIBROAWWMDJ-OAHLLOKOSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- GZNZXLRJPJOBAY-UHFFFAOYSA-N 2-(azetidin-3-yl)-5-(6-fluoro-1H-indol-3-yl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound N1CC(C1)N1S(C2=C(C1)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O GZNZXLRJPJOBAY-UHFFFAOYSA-N 0.000 claims 1
- QCIJWHDJHWUKCI-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]-N,N-dimethylethanamine Chemical compound CN(CCN1S(C2=C(C1)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O)C QCIJWHDJHWUKCI-UHFFFAOYSA-N 0.000 claims 1
- ZKBOYHOLKWEZTJ-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]ethanamine Chemical compound NCCN1S(C2=C(C1)C=C(C=C2)C1=CNC2=CC(=CC=C12)F)(=O)=O ZKBOYHOLKWEZTJ-UHFFFAOYSA-N 0.000 claims 1
- CRIMTKLPICUTMT-UHFFFAOYSA-N 2-[5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-3H-1,2-benzothiazol-2-yl]ethanol Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)CCO)C=1 CRIMTKLPICUTMT-UHFFFAOYSA-N 0.000 claims 1
- VFYDGJNCGAVMBU-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-2-(1-methylazetidin-3-yl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)C2CN(C2)C)C=1 VFYDGJNCGAVMBU-UHFFFAOYSA-N 0.000 claims 1
- ITQMDQPZQGQNHV-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-2-(1-methylpiperidin-4-yl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)C2CCN(CC2)C)C=1 ITQMDQPZQGQNHV-UHFFFAOYSA-N 0.000 claims 1
- PFODQNCZTNXHQC-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-2-(2-methylsulfinylethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)CCS(=O)C)C=1 PFODQNCZTNXHQC-UHFFFAOYSA-N 0.000 claims 1
- WUYBEIGQZMXBMJ-OAHLLOKOSA-N 5-(6-fluoro-1H-indol-3-yl)-2-[(3R)-oxolan-3-yl]-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)[C@H]2COCC2)C=1 WUYBEIGQZMXBMJ-OAHLLOKOSA-N 0.000 claims 1
- WUYBEIGQZMXBMJ-HNNXBMFYSA-N 5-(6-fluoro-1H-indol-3-yl)-2-[(3S)-oxolan-3-yl]-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)[C@@H]2COCC2)C=1 WUYBEIGQZMXBMJ-HNNXBMFYSA-N 0.000 claims 1
- YULQEZKKXGNCKE-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-2-piperidin-4-yl-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(CN(S2(=O)=O)C2CCNCC2)C=1 YULQEZKKXGNCKE-UHFFFAOYSA-N 0.000 claims 1
- OWTRVSZKMCEMPJ-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3,3-dimethyl-2H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)(C)C)C=1 OWTRVSZKMCEMPJ-UHFFFAOYSA-N 0.000 claims 1
- GWMPFYQTAPDESW-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(=NS2(=O)=O)C)C=1 GWMPFYQTAPDESW-UHFFFAOYSA-N 0.000 claims 1
- YNVGNSUTDNJJNH-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-(pyridin-2-ylmethyl)-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CC2=NC=CC=C2)C)C=1 YNVGNSUTDNJJNH-UHFFFAOYSA-N 0.000 claims 1
- GZACIBROAWWMDJ-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)-3-methyl-2-[(6-methylpyridin-2-yl)methyl]-3H-1,2-benzothiazole 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CC2=NC(=CC=C2)C)C)C=1 GZACIBROAWWMDJ-UHFFFAOYSA-N 0.000 claims 1
- BMJVEMOJJOLGAB-UHFFFAOYSA-N 5-(6-fluoro-1H-indol-3-yl)spiro[2H-1,2-benzothiazole-3,1'-cyclopropane] 1,1-dioxide Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C=1)C1(CC1)NS2(=O)=O BMJVEMOJJOLGAB-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- WYKSGEFWOINIQZ-UHFFFAOYSA-N FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCN2N=C(C=C2O)C)C)C=1 Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(N(S2(=O)=O)CCN2N=C(C=C2O)C)C)C=1 WYKSGEFWOINIQZ-UHFFFAOYSA-N 0.000 claims 1
- 101000892398 Homo sapiens Tryptophan 2,3-dioxygenase Proteins 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010027406 Mesothelioma Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000006265 Renal cell carcinoma Diseases 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- SASRMTYDFPRPRU-UHFFFAOYSA-N methyl 5-(6-fluoro-1H-indol-3-yl)-1,1-dioxo-2,3-dihydro-1,2-benzothiazole-3-carboxylate Chemical compound FC1=CC=C2C(=CNC2=C1)C=1C=CC2=C(C(NS2(=O)=O)C(=O)OC)C=1 SASRMTYDFPRPRU-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB2015/051957 WO2015140717A1 (en) | 2014-03-18 | 2015-03-17 | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| IBPCT/IB2015/051957 | 2015-03-17 | ||
| US201562203032P | 2015-08-10 | 2015-08-10 | |
| US62/203,032 | 2015-08-10 | ||
| PCT/IB2016/051509 WO2016147144A1 (en) | 2015-03-17 | 2016-03-17 | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018511587A JP2018511587A (ja) | 2018-04-26 |
| JP2018511587A5 true JP2018511587A5 (enExample) | 2019-04-25 |
| JP6775516B2 JP6775516B2 (ja) | 2020-10-28 |
Family
ID=56919874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017548261A Expired - Fee Related JP6775516B2 (ja) | 2015-03-17 | 2016-03-17 | 新奇な３−インドール置換誘導体、医薬組成物、および使用方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9873690B2 (enExample) |
| EP (1) | EP3271354A1 (enExample) |
| JP (1) | JP6775516B2 (enExample) |
| KR (1) | KR102013512B1 (enExample) |
| CN (1) | CN107635990A (enExample) |
| AU (1) | AU2016231832B2 (enExample) |
| BR (1) | BR112017019699A2 (enExample) |
| CA (1) | CA2979616C (enExample) |
| HK (1) | HK1243999A1 (enExample) |
| IL (1) | IL254124A0 (enExample) |
| MX (1) | MX2017011951A (enExample) |
| RU (1) | RU2672252C1 (enExample) |
| SG (1) | SG11201706992TA (enExample) |
| WO (1) | WO2016147144A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160336813A1 (en) | 2015-05-15 | 2016-11-17 | NeuSpera Medical Inc. | Midfield coupler |
| EP4074273A1 (en) | 2014-05-18 | 2022-10-19 | NeuSpera Medical Inc. | Midfield coupler |
| KR101997241B1 (ko) | 2015-05-21 | 2019-07-09 | 하푼 테라퓨틱스, 인크. | 삼중특이성 결합 단백질 및 사용 방법 |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| EP3554494A4 (en) | 2016-12-19 | 2021-02-17 | Cellixbio Private Limited | COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATION |
| AU2018265856B2 (en) | 2017-05-12 | 2023-04-27 | Harpoon Therapeutics, Inc. | Mesothelin binding proteins |
| CA3060989A1 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising a combination of an anti-lag-3 antibody, a pd-1 pathway inhibitor, and an immunotherapeutic agent |
| WO2019075359A1 (en) | 2017-10-13 | 2019-04-18 | Harpoon Therapeutics, Inc. | TRISPECIFIC PROTEINS AND METHODS OF USE |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| US12195544B2 (en) | 2018-09-21 | 2025-01-14 | Harpoon Therapeutics, Inc. | EGFR binding proteins and methods of use |
| BR112021005769A2 (pt) | 2018-09-25 | 2021-07-06 | Harpoon Therapeutics Inc | proteínas de ligação a dll3 e métodos de uso |
| WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
| CN111166735B (zh) * | 2020-01-15 | 2023-08-18 | 延边大学 | 邻苯二甲酸-双-(2-乙基庚基)酯在抑制脂肪蓄积中的应用 |
| CN111499592B (zh) * | 2020-03-14 | 2023-06-23 | 江苏省农用激素工程技术研究中心有限公司 | 5-氨甲基糖精的合成方法 |
| JP7296017B2 (ja) | 2020-04-30 | 2023-06-21 | メッドシャイン ディスカバリー インコーポレイテッド | ベンゾスルタムを含む化合物 |
| CA3182579A1 (en) | 2020-07-07 | 2022-01-13 | Ugur Sahin | Therapeutic rna for hpv-positive cancer |
| CN111777557B (zh) * | 2020-07-28 | 2022-11-22 | 中国科学院上海有机化学研究所 | 以芳香联苯烯为骨架的新型抗肿瘤先导化合物及其应用 |
| WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
| WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
| TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性ｒｎａ |
| MX2024000674A (es) | 2021-07-13 | 2024-02-07 | BioNTech SE | Agentes de union multiespecificos contra cd40 y cd137 en terapia de combinacion. |
| TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
| CN119156403A (zh) | 2022-03-08 | 2024-12-17 | 阿伦蒂斯治疗股份公司 | 抗紧密连接蛋白-1抗体增加t细胞可用性的用途 |
| IL321098A (en) | 2022-12-14 | 2025-07-01 | Astellas Pharma Europe Bv | Combination therapy including bispecific binding agents that bind to CLDN18.2- and CD3- and immune checkpoint inhibitors |
| WO2025121445A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| WO2025120867A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and anti-vegfr2 antibodies |
| WO2025120866A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| CN119707855A (zh) * | 2024-12-20 | 2025-03-28 | 西南大学 | 一种光学活性胺类衍生物及其不对称烷基化合成方法和应用 |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE509731C2 (sv) | 1996-05-14 | 1999-03-01 | Labwell Ab | Metod för palladium-katalyserade organiska reaktioner innefattande ett uppvärmningssteg utfört med mikrovågsenergi |
| JP2000095759A (ja) | 1998-07-21 | 2000-04-04 | Takeda Chem Ind Ltd | 三環性化合物、その製造法および剤 |
| US6265403B1 (en) | 1999-01-20 | 2001-07-24 | Merck & Co., Inc. | Angiogenesis inhibitors |
| BR0212613A (pt) | 2001-09-19 | 2004-08-31 | Pharmacia Corp | Compostos de indazol substituìdos para o tratamento de inflamação |
| DE60331219D1 (de) | 2002-03-28 | 2010-03-25 | Eisai R&D Man Co Ltd | Azaindole als hemmstoffe von c-jun n-terminalen kinasen |
| TW200307542A (en) | 2002-05-30 | 2003-12-16 | Astrazeneca Ab | Novel compounds |
| FR2845996A1 (fr) | 2002-10-16 | 2004-04-23 | Servier Lab | Nouveaux derives de[3,4-a:3,4-c]carbazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN1794986B (zh) * | 2003-03-27 | 2012-09-05 | 兰肯瑙医学研究所 | 治疗癌症的新药物 |
| EP1606285A4 (en) * | 2003-03-27 | 2009-03-18 | Lankenau Inst Medical Res | NEW IDO HEMMER AND APPLICATION PROCEDURES |
| FR2862647B1 (fr) | 2003-11-25 | 2008-07-04 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
| GB0328909D0 (en) | 2003-12-12 | 2004-01-14 | Syngenta Participations Ag | Chemical compounds |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| EP1805171A4 (en) * | 2004-09-21 | 2009-05-13 | Wyeth Corp | CRTH2 RECEPTOR ANTAGONISM DISPLAYING INDIGENOUS ACIDS AND APPLICATIONS THEREOF |
| NZ560225A (en) | 2005-02-09 | 2010-10-29 | Arqule Inc | Maleimide derivatives, pharmaceutical compositions and methods for treatment of cancer |
| WO2007039580A1 (en) | 2005-10-05 | 2007-04-12 | Nycomed Gmbh | Imidazolyl-substituted benzophenone compounds |
| WO2007045622A1 (en) | 2005-10-18 | 2007-04-26 | Nycomed Gmbh | Oxazolo [4 , 5-b] pyridine compounds as nitric oxide synthase inhibitors |
| WO2007050963A1 (en) * | 2005-10-27 | 2007-05-03 | Lankenau Institute For Medical Research | Novel ido inhibitors and methods of use thereof |
| CN101374808B (zh) | 2006-01-24 | 2011-05-25 | 伊莱利利公司 | 孕酮受体的吲哚磺酰胺调节剂 |
| US8008481B2 (en) | 2006-03-31 | 2011-08-30 | Ericsson Anna M | Indazole compounds |
| KR20080108517A (ko) | 2006-04-05 | 2008-12-15 | 노파르티스 아게 | 암을 치료하기 위한 치료제의 조합물 |
| GB0624308D0 (en) | 2006-12-05 | 2007-01-17 | Molmed Spa | Combination product |
| US8058272B2 (en) | 2006-12-07 | 2011-11-15 | Novartis Ag | Organic compounds |
| CA2677096A1 (en) | 2007-01-31 | 2008-08-07 | Vertex Pharmaceuticals Incorporated | Kinase inhibitors |
| EP2137168B1 (en) * | 2007-03-16 | 2016-09-14 | Lankenau Institute for Medical Research | Novel ido inhibitors and methods of use thereof |
| CA2694224A1 (en) | 2007-07-25 | 2009-01-29 | Boehringer Ingelheim International Gmbh | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7868001B2 (en) | 2007-11-02 | 2011-01-11 | Hutchison Medipharma Enterprises Limited | Cytokine inhibitors |
| JP2011508725A (ja) | 2007-11-30 | 2011-03-17 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | プロリルヒドロキシラーゼ阻害剤 |
| AU2009228765B2 (en) | 2008-03-24 | 2012-05-31 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
| US20110159017A1 (en) | 2008-04-11 | 2011-06-30 | Ludwig Institute For Cancer Research Ltd. | Trytophan catabolism in cancer treatment and diagnosis |
| NZ590268A (en) * | 2008-07-08 | 2012-11-30 | Incyte Corp | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
| DE102008052943A1 (de) | 2008-10-23 | 2010-04-29 | Merck Patent Gmbh | Azaindolderivate |
| US8084620B2 (en) | 2008-12-19 | 2011-12-27 | Bristol-Myers Squibb Company | Carbazole carboxamide compounds useful as kinase inhibitors |
| WO2010096389A1 (en) | 2009-02-17 | 2010-08-26 | Vertex Pharmaceuticals Incorporated | Tetrahydrothiazolopyridine inhibitors of phosphatidylinositol 3-kinase |
| US8158625B2 (en) | 2009-05-27 | 2012-04-17 | Genentech, Inc. | Bicyclic indole-pyrimidine PI3K inhibitor compounds selective for P110 delta, and methods of use |
| KR101256018B1 (ko) | 2009-08-20 | 2013-04-18 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 갖는 1,3,6-치환된 인돌 화합물 |
| AU2010298168B2 (en) | 2009-09-23 | 2015-11-19 | Medivation Technologies, Inc. | Pyrido(3,4-b)indoles and methods of use |
| BR112012006956A2 (pt) | 2009-10-12 | 2015-09-15 | Bayer Cropscience Ag | 1- (pirida-3-il) -pirazóisol e 1- (pirimida-5-il) - pirazóisol como pesticidas |
| CN102656141B (zh) | 2009-10-13 | 2016-04-06 | 利亘制药公司 | 模拟造血生长因子的小分子化合物及其用途 |
| CN103282034A (zh) | 2010-11-18 | 2013-09-04 | 利亘制药公司 | 造血生长因子模拟物的用途 |
| AU2012230890A1 (en) | 2011-03-22 | 2013-09-26 | Amgen Inc. | Azole compounds as Pim inhibitors |
| US9273029B2 (en) | 2011-05-23 | 2016-03-01 | Merck Patent Gmbh | Pyridine-and pyrazine derivatives |
| EP2744805A1 (en) | 2011-08-17 | 2014-06-25 | Amgen Inc. | Heteroaryl sodium channel inhibitors |
| US20160263087A1 (en) | 2013-11-08 | 2016-09-15 | Iteos Therapeutics | Novel 4-(indol-3-yl)-pyrazole derivatives, pharmaceutical compositions and methods for use |
| US9126984B2 (en) | 2013-11-08 | 2015-09-08 | Iteos Therapeutics | 4-(indol-3-yl)-pyrazole derivatives, pharmaceutical compositions and methods for use |
| JP2017505346A (ja) | 2014-02-12 | 2017-02-16 | アイティーオス セラペウティクス | 新規な３−（インドール−３−イル）−ピリジン誘導体、医薬組成物、および使用方法 |
| US20150266857A1 (en) * | 2014-03-18 | 2015-09-24 | Iteos Therapeutics | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| CA2942761A1 (en) * | 2014-03-18 | 2015-09-24 | Iteos Therapeutics | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| SG11201608708WA (en) | 2014-05-15 | 2016-11-29 | Iteos Therapeutics | Pyrrolidine-2,5-dione derivatives, pharmaceutical compositions and methods for use as ido1 inhibitors |
| CA2994917A1 (en) * | 2015-08-10 | 2017-02-16 | Pfizer Inc. | 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
-
2016
- 2016-03-17 WO PCT/IB2016/051509 patent/WO2016147144A1/en not_active Ceased
- 2016-03-17 BR BR112017019699-9A patent/BR112017019699A2/pt not_active Application Discontinuation
- 2016-03-17 SG SG11201706992TA patent/SG11201706992TA/en unknown
- 2016-03-17 MX MX2017011951A patent/MX2017011951A/es unknown
- 2016-03-17 HK HK18103418.8A patent/HK1243999A1/zh unknown
- 2016-03-17 CN CN201680028408.7A patent/CN107635990A/zh active Pending
- 2016-03-17 RU RU2017130845A patent/RU2672252C1/ru not_active IP Right Cessation
- 2016-03-17 US US15/072,534 patent/US9873690B2/en not_active Expired - Fee Related
- 2016-03-17 CA CA2979616A patent/CA2979616C/en not_active Expired - Fee Related
- 2016-03-17 KR KR1020177029203A patent/KR102013512B1/ko not_active Expired - Fee Related
- 2016-03-17 JP JP2017548261A patent/JP6775516B2/ja not_active Expired - Fee Related
- 2016-03-17 AU AU2016231832A patent/AU2016231832B2/en not_active Ceased
- 2016-03-17 EP EP16711022.0A patent/EP3271354A1/en not_active Withdrawn
-
2017
- 2017-08-23 IL IL254124A patent/IL254124A0/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018511587A5 (enExample) | ||
| JP2018527336A5 (enExample) | ||
| RU2012134306A (ru) | Азотосодержащие производные гетероарилов | |
| JP2007519754A5 (enExample) | ||
| JP2017530185A5 (enExample) | ||
| JP2017505762A5 (enExample) | ||
| JP2005526723A5 (enExample) | ||
| JP2007505922A5 (enExample) | ||
| JP2006206609A5 (enExample) | ||
| JP2020512373A5 (enExample) | ||
| JP2010524896A5 (enExample) | ||
| JP2012520238A5 (enExample) | ||
| JP2018522032A5 (enExample) | ||
| JP2010526800A5 (enExample) | ||
| JP2020502092A5 (enExample) | ||
| JP2011526616A5 (enExample) | ||
| JP2018524338A5 (enExample) | ||
| JP2013525438A5 (enExample) | ||
| HRP20201469T1 (hr) | Derivati tetrahidroizokinolina | |
| RU2007124545A (ru) | Производные [4-(гетероарил)пиперазин-1-ил]-(2,5-замещенный фенил)метанона в качестве ингибиторов переносчика глицина-1 (glyt-1) для лечения неврологических и психоневрологических заболеваний | |
| JP2007519695A5 (enExample) | ||
| JP2014523400A5 (enExample) | ||
| JP2008500999A5 (enExample) | ||
| JP2010524899A5 (enExample) | ||
| JP2013517279A5 (enExample) |