HRP20231734T1 - Triciklički akr1c3 ovisni kars inhibitori - Google Patents
Triciklički akr1c3 ovisni kars inhibitori Download PDFInfo
- Publication number
- HRP20231734T1 HRP20231734T1 HRP20231734TT HRP20231734T HRP20231734T1 HR P20231734 T1 HRP20231734 T1 HR P20231734T1 HR P20231734T T HRP20231734T T HR P20231734TT HR P20231734 T HRP20231734 T HR P20231734T HR P20231734 T1 HRP20231734 T1 HR P20231734T1
- Authority
- HR
- Croatia
- Prior art keywords
- fluoro
- spiro
- quinoline
- dihydro
- carboxamide
- Prior art date
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- 230000001419 dependent effect Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 18
- 150000001875 compounds Chemical class 0.000 claims 18
- 229910052736 halogen Inorganic materials 0.000 claims 11
- 125000005843 halogen group Chemical group 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 125000000217 alkyl group Chemical group 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 125000000623 heterocyclic group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- WILXKPUUUNCWJW-NSCUHMNNSA-N 1-[(E)-but-2-enyl]-6-fluoro-N-[(4-fluorophenyl)methyl]-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(\C=C\C)N1C2(CC(C3=CC(=CC=C13)F)=O)CCN(CC2)C(=O)NCC1=CC=C(C=C1)F WILXKPUUUNCWJW-NSCUHMNNSA-N 0.000 claims 2
- OIHWXKWJYJDZSC-UHFFFAOYSA-N 1-ethyl-6-fluoro-N-[(4-fluorophenyl)methyl]-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(C)N1C2(CC(C3=CC(=CC=C13)F)=O)CCN(CC2)C(=O)NCC1=CC=C(C=C1)F OIHWXKWJYJDZSC-UHFFFAOYSA-N 0.000 claims 2
- YZMWJEDIULFHRX-UHFFFAOYSA-N 1-ethyl-6-fluoro-N-[[4-fluoro-3-(2-hydroxyethylamino)phenyl]methyl]-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(C)N1C2(CC(C3=CC(=CC=C13)F)=O)CCN(CC2)C(=O)NCC1=CC(=C(C=C1)F)NCCO YZMWJEDIULFHRX-UHFFFAOYSA-N 0.000 claims 2
- QKIRIBPTXYDKAH-UHFFFAOYSA-N 6,8-difluoro-4-oxo-N-[[3-(1,2,4-triazol-1-yl)phenyl]methyl]spiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N1(N=CN=C1)C=1C=C(CNC(=O)N2CCC3(NC4=C(C=C(C=C4C(C3)=O)F)F)CC2)C=CC=1 QKIRIBPTXYDKAH-UHFFFAOYSA-N 0.000 claims 2
- ILVAMWYWJXZVBG-UHFFFAOYSA-N 6,8-difluoro-N-(furan-3-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=COC=C1)=O ILVAMWYWJXZVBG-UHFFFAOYSA-N 0.000 claims 2
- PPGHIHYCIKVZQV-UHFFFAOYSA-N 6,8-difluoro-N-[(2-methoxypyridin-4-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=CC(=NC=C1)OC)=O PPGHIHYCIKVZQV-UHFFFAOYSA-N 0.000 claims 2
- AJLZTCVWMUVWTP-UHFFFAOYSA-N 6,8-difluoro-N-[(2-methylfuran-3-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=C(OC=C1)C)=O AJLZTCVWMUVWTP-UHFFFAOYSA-N 0.000 claims 2
- NVFUUXCXWSCALH-UHFFFAOYSA-N 6,8-difluoro-N-[(3-hydroxypyridin-2-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=NC=CC=C1O)=O NVFUUXCXWSCALH-UHFFFAOYSA-N 0.000 claims 2
- HNRMFLGMCHCHEL-UHFFFAOYSA-N 6,8-difluoro-N-[(4-hydroxyphenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=CC=C(C=C1)O)=O HNRMFLGMCHCHEL-UHFFFAOYSA-N 0.000 claims 2
- MEBQWURAVKNEKJ-UHFFFAOYSA-N 6,8-difluoro-N-[(5-methylthiophen-2-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC=1SC(=CC=1)C)=O MEBQWURAVKNEKJ-UHFFFAOYSA-N 0.000 claims 2
- NFYUIXXRWLAGOP-UHFFFAOYSA-N 6,8-difluoro-N-[(6-fluoropyridin-3-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC=1C=NC(=CC=1)F)=O NFYUIXXRWLAGOP-UHFFFAOYSA-N 0.000 claims 2
- FXXZVTGUUBWFQY-UHFFFAOYSA-N 6,8-difluoro-N-[[3-(1,3-oxazol-5-yl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=CC(=CC=C1)C1=CN=CO1)=O FXXZVTGUUBWFQY-UHFFFAOYSA-N 0.000 claims 2
- DLTMRJADLQKBPO-UHFFFAOYSA-N 6,8-difluoro-N-[[3-(hydroxymethyl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=CC(=CC=C1)CO)=O DLTMRJADLQKBPO-UHFFFAOYSA-N 0.000 claims 2
- GKUZLEIKYLPYKR-UHFFFAOYSA-N 6,8-difluoro-N-[[4-fluoro-3-(hydroxymethyl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=C(C=1)F)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)CO)=O GKUZLEIKYLPYKR-UHFFFAOYSA-N 0.000 claims 2
- MUTXPYJCJPWLDX-UHFFFAOYSA-N 6-fluoro-1-methyl-N-[(5-methylfuran-2-yl)methyl]-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC=1OC(=CC=1)C)=O MUTXPYJCJPWLDX-UHFFFAOYSA-N 0.000 claims 2
- JYLDFKRXZXXILA-UHFFFAOYSA-N 6-fluoro-4-oxo-N-(1H-pyrazol-4-ylmethyl)spiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N1N=CC(=C1)CNC(=O)N1CCC2(NC3=CC=C(C=C3C(C2)=O)F)CC1 JYLDFKRXZXXILA-UHFFFAOYSA-N 0.000 claims 2
- XYTQGHYLVJLGRT-UHFFFAOYSA-N 6-fluoro-4-oxo-N-(1H-pyrazol-5-ylmethyl)spiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N1N=C(C=C1)CNC(=O)N1CCC2(NC3=CC=C(C=C3C(C2)=O)F)CC1 XYTQGHYLVJLGRT-UHFFFAOYSA-N 0.000 claims 2
- KBICXKUPHXIHMV-UHFFFAOYSA-N 6-fluoro-4-oxo-N-[(3-sulfamoylphenyl)methyl]spiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=CC=C1)S(N)(=O)=O)=O KBICXKUPHXIHMV-UHFFFAOYSA-N 0.000 claims 2
- FKFFREACDMRMBQ-UHFFFAOYSA-N 6-fluoro-4-oxo-N-[[2-(trifluoromethyl)furan-3-yl]methyl]spiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(OC=C1)C(F)(F)F)=O FKFFREACDMRMBQ-UHFFFAOYSA-N 0.000 claims 2
- LSEJYNNMMVDSDU-UHFFFAOYSA-N 6-fluoro-N-(1,2-oxazol-3-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=NOC=C1)=O LSEJYNNMMVDSDU-UHFFFAOYSA-N 0.000 claims 2
- OTLMBIUXYHVJKK-UHFFFAOYSA-N 6-fluoro-N-(1,2-oxazol-4-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC=1C=NOC=1)=O OTLMBIUXYHVJKK-UHFFFAOYSA-N 0.000 claims 2
- JOFCQZWOQLLRRF-UHFFFAOYSA-N 6-fluoro-N-(1,2-oxazol-5-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC=NO1)=O JOFCQZWOQLLRRF-UHFFFAOYSA-N 0.000 claims 2
- MBDHNRIZEWPGHL-UHFFFAOYSA-N 6-fluoro-N-(1,3-oxazol-4-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC=1N=COC=1)=O MBDHNRIZEWPGHL-UHFFFAOYSA-N 0.000 claims 2
- LCTUIJFBIJQNHI-UHFFFAOYSA-N 6-fluoro-N-(1H-indol-6-ylmethyl)-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N1C=CC2=CC=C(C=C12)CNC(=O)N1CCC2(NC3=CC=C(C=C3C(C2)=O)F)CC1 LCTUIJFBIJQNHI-UHFFFAOYSA-N 0.000 claims 2
- NXLXHTBFHYUFHP-UHFFFAOYSA-N 6-fluoro-N-[(1-methylpyrazol-4-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC=1C=NN(C=1)C)=O NXLXHTBFHYUFHP-UHFFFAOYSA-N 0.000 claims 2
- PPHRIVJUFVOBOE-UHFFFAOYSA-N 6-fluoro-N-[(2-methylfuran-3-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(OC=C1)C)=O PPHRIVJUFVOBOE-UHFFFAOYSA-N 0.000 claims 2
- JLPPUKLSPYGNRB-UHFFFAOYSA-N 6-fluoro-N-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=NC(=NO1)C)=O JLPPUKLSPYGNRB-UHFFFAOYSA-N 0.000 claims 2
- FOKADWKBVVGPFG-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-2-hydroxyphenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)O)=O FOKADWKBVVGPFG-UHFFFAOYSA-N 0.000 claims 2
- IRMXLYDFDWFBQZ-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-2-methoxyphenyl)methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)OC)=O IRMXLYDFDWFBQZ-UHFFFAOYSA-N 0.000 claims 2
- INSJSEYDCIHRRG-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-2-methoxyphenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)OC)=O INSJSEYDCIHRRG-UHFFFAOYSA-N 0.000 claims 2
- PESBKESWZSCILB-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-3-methoxyphenyl)methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)OC)=O PESBKESWZSCILB-UHFFFAOYSA-N 0.000 claims 2
- PAOWPUJZOYULQR-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-3-sulfamoylphenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)S(N)(=O)=O)=O PAOWPUJZOYULQR-UHFFFAOYSA-N 0.000 claims 2
- ZODRYECWZWJLJX-UHFFFAOYSA-N 6-fluoro-N-[(4-fluorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)CCO)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)=O ZODRYECWZWJLJX-UHFFFAOYSA-N 0.000 claims 2
- YZIHFCAFAGLLNH-UHFFFAOYSA-N 6-fluoro-N-[(4-fluorophenyl)methyl]-1-(2-methoxyethyl)-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)CCOC)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)=O YZIHFCAFAGLLNH-UHFFFAOYSA-N 0.000 claims 2
- WVZQZRVDIMHSMC-UHFFFAOYSA-N 6-fluoro-N-[(4-fluorophenyl)methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)=O WVZQZRVDIMHSMC-UHFFFAOYSA-N 0.000 claims 2
- TYINSPYSAGQHRJ-UHFFFAOYSA-N 6-fluoro-N-[(4-fluorophenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)=O TYINSPYSAGQHRJ-UHFFFAOYSA-N 0.000 claims 2
- MZIATKFUXPUFAI-UHFFFAOYSA-N 6-fluoro-N-[(4-hydroxyphenyl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC=C(C=C1)O)=O MZIATKFUXPUFAI-UHFFFAOYSA-N 0.000 claims 2
- OGHMDZXRKOQOIQ-UHFFFAOYSA-N 6-fluoro-N-[(5-methyl-1H-pyrazol-3-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=NNC(=C1)C)=O OGHMDZXRKOQOIQ-UHFFFAOYSA-N 0.000 claims 2
- PUAGCJNOVIUTMH-UHFFFAOYSA-N 6-fluoro-N-[(5-methylfuran-2-yl)methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC=1OC(=CC=1)C)=O PUAGCJNOVIUTMH-UHFFFAOYSA-N 0.000 claims 2
- ZVGJKWFCFFMOLS-UHFFFAOYSA-N 6-fluoro-N-[[3-(1H-imidazol-2-yl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N1C(=NC=C1)C=1C=C(CNC(=O)N2CCC3(NC4=CC=C(C=C4C(C3)=O)F)CC2)C=CC=1 ZVGJKWFCFFMOLS-UHFFFAOYSA-N 0.000 claims 2
- WJHIIAJSTFBIHK-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)OCC(F)(F)F)=O WJHIIAJSTFBIHK-UHFFFAOYSA-N 0.000 claims 2
- JRENCXPQWFQBTF-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-2-(2-hydroxyethylamino)phenyl]methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)NCCO)=O JRENCXPQWFQBTF-UHFFFAOYSA-N 0.000 claims 2
- UTTMXMULCDUQGC-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-2-(2-methoxyethylamino)phenyl]methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)NCCOC)=O UTTMXMULCDUQGC-UHFFFAOYSA-N 0.000 claims 2
- RBFBBOIKZFSORM-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)C(F)(F)F)=O RBFBBOIKZFSORM-UHFFFAOYSA-N 0.000 claims 2
- IMJDEYGVMRSAPU-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(1,3-oxazol-5-yl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)C1=CN=CO1)=O IMJDEYGVMRSAPU-UHFFFAOYSA-N 0.000 claims 2
- UKNQEBGLGBSODW-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(1-hydroxyethyl)phenyl]methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)C(C)O)=O UKNQEBGLGBSODW-UHFFFAOYSA-N 0.000 claims 2
- ADMGUGQFYOJARP-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(1-hydroxyethyl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)C(C)O)=O ADMGUGQFYOJARP-UHFFFAOYSA-N 0.000 claims 2
- WUYXLXHGKICOER-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2,2,2-trifluoroethylcarbamoyl)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)C(NCC(F)(F)F)=O)=O WUYXLXHGKICOER-UHFFFAOYSA-N 0.000 claims 2
- AUBDRARVPTWYGL-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2-hydroxyethoxy)phenyl]methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)OCCO)=O AUBDRARVPTWYGL-UHFFFAOYSA-N 0.000 claims 2
- GFLUASGUKQDJDF-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2-hydroxyethoxy)phenyl]methyl]-4-oxospiro[1,3-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)OCCO)=O GFLUASGUKQDJDF-UHFFFAOYSA-N 0.000 claims 2
- FENXJYUIJWZXHS-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2-hydroxyethylamino)phenyl]methyl]-1-methyl-4-oxospiro[3H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)NCCO)=O FENXJYUIJWZXHS-UHFFFAOYSA-N 0.000 claims 2
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- QAXPDNCPOKVFAO-IBGZPJMESA-N (4S)-6-fluoro-N-[(4-fluoro-2-hydroxyphenyl)methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2[C@H](CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)O)O QAXPDNCPOKVFAO-IBGZPJMESA-N 0.000 claims 1
- BEXOOGBNLOIQSW-FQEVSTJZSA-N (4S)-6-fluoro-N-[(4-fluorophenyl)methyl]-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2[C@H](CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)O BEXOOGBNLOIQSW-FQEVSTJZSA-N 0.000 claims 1
- NFSDYHWRSBUJPB-IBGZPJMESA-N (4S)-6-fluoro-N-[(4-fluorophenyl)methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2[C@H](CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC=C(C=C1)F)O NFSDYHWRSBUJPB-IBGZPJMESA-N 0.000 claims 1
- VFXSKNOLUYPSLS-IBGZPJMESA-N (4S)-N-[(4-amino-3-fluorophenyl)methyl]-6-fluoro-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound NC1=C(C=C(CNC(=O)N2CCC3(NC4=CC=C(C=C4[C@H](C3)O)F)CC2)C=C1)F VFXSKNOLUYPSLS-IBGZPJMESA-N 0.000 claims 1
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 1
- IJFYKDVVNZQHFR-UHFFFAOYSA-N 6-fluoro-N-[(4-fluoro-2-methoxyphenyl)methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)OC)O IJFYKDVVNZQHFR-UHFFFAOYSA-N 0.000 claims 1
- YLYVCNHZIOIQBC-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-2-(2-methoxyethylamino)phenyl]methyl]-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=C(C=C(C=C1)F)NCCOC)O YLYVCNHZIOIQBC-UHFFFAOYSA-N 0.000 claims 1
- SAXBYGKRPXQNHK-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2-hydroxyethoxy)phenyl]methyl]-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)OCCO)O SAXBYGKRPXQNHK-UHFFFAOYSA-N 0.000 claims 1
- PQCLOIQDOBTGAD-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(2-hydroxyethylamino)phenyl]methyl]-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(N(C2=CC=1)C)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)NCCO)O PQCLOIQDOBTGAD-UHFFFAOYSA-N 0.000 claims 1
- JPLKLHBOBQFLOC-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(hydroxymethyl)phenyl]methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)CO)O JPLKLHBOBQFLOC-UHFFFAOYSA-N 0.000 claims 1
- VGVPDIGXYRCVHT-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-(methanesulfonamido)phenyl]methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)NS(=O)(=O)C)O VGVPDIGXYRCVHT-UHFFFAOYSA-N 0.000 claims 1
- HEEVRWWTCGDGHC-UHFFFAOYSA-N 6-fluoro-N-[[4-fluoro-3-[(3-hydroxycyclobutyl)carbamoyl]phenyl]methyl]-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC=1C=C2C(CC3(NC2=CC=1)CCN(CC3)C(=O)NCC1=CC(=C(C=C1)F)C(NC1CC(C1)O)=O)O HEEVRWWTCGDGHC-UHFFFAOYSA-N 0.000 claims 1
- 101150028310 AKR1C3 gene Proteins 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 102100028908 Cullin-3 Human genes 0.000 claims 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 101000916238 Homo sapiens Cullin-3 Proteins 0.000 claims 1
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims 1
- 108091007984 KARS Proteins 0.000 claims 1
- 102000004034 Kelch-Like ECH-Associated Protein 1 Human genes 0.000 claims 1
- 108090000484 Kelch-Like ECH-Associated Protein 1 Proteins 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 102100035529 Lysine-tRNA ligase Human genes 0.000 claims 1
- OPRFQHGUIIDGGJ-UHFFFAOYSA-N N-[(3-amino-4-fluorophenyl)methyl]-6-fluoro-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound NC=1C=C(CNC(=O)N2CCC3(NC4=CC=C(C=C4C(C3)O)F)CC2)C=CC=1F OPRFQHGUIIDGGJ-UHFFFAOYSA-N 0.000 claims 1
- JYMMFJCQURIXBN-UHFFFAOYSA-N N-[(3-carbamoyl-4-fluorophenyl)methyl]-6,8-difluoro-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(N)(=O)C=1C=C(CNC(=O)N2CCC3(NC4=C(C=C(C=C4C(C3)O)F)F)CC2)C=CC=1F JYMMFJCQURIXBN-UHFFFAOYSA-N 0.000 claims 1
- DMLTXXUWFXZAOF-UHFFFAOYSA-N N-[(3-carbamoyl-4-fluorophenyl)methyl]-6-fluoro-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(N)(=O)C=1C=C(CNC(=O)N2CCC3(N(C4=CC=C(C=C4C(C3)O)F)C)CC2)C=CC=1F DMLTXXUWFXZAOF-UHFFFAOYSA-N 0.000 claims 1
- RUWKGISDBSMALH-UHFFFAOYSA-N N-[(3-carbamoyl-4-fluorophenyl)methyl]-6-fluoro-4-hydroxyspiro[3,4-dihydro-1H-quinoline-2,4'-piperidine]-1'-carboxamide Chemical compound C(N)(=O)C=1C=C(CNC(=O)N2CCC3(NC4=CC=C(C=C4C(C3)O)F)CC2)C=CC=1F RUWKGISDBSMALH-UHFFFAOYSA-N 0.000 claims 1
- ZIBFXAXUTUVYBH-UHFFFAOYSA-N N-[[2,4-difluoro-5-(2-hydroxyethylamino)phenyl]methyl]-6-fluoro-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound FC1=C(CNC(=O)N2CCC3(N(C4=CC=C(C=C4C(C3)O)F)C)CC2)C=C(C(=C1)F)NCCO ZIBFXAXUTUVYBH-UHFFFAOYSA-N 0.000 claims 1
- DREYIEFLPJIXKJ-UHFFFAOYSA-N N-[[3-(2-amino-2-oxoethyl)-4-fluorophenyl]methyl]-6-fluoro-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound NC(CC=1C=C(CNC(=O)N2CCC3(N(C4=CC=C(C=C4C(C3)O)F)C)CC2)C=CC=1F)=O DREYIEFLPJIXKJ-UHFFFAOYSA-N 0.000 claims 1
- OSUAIFHDIUGTQU-BPGUCPLFSA-N N-[[3-[(1R)-1-amino-2,2,2-trifluoroethyl]-4-fluorophenyl]methyl]-6-fluoro-4-hydroxy-1-methylspiro[3,4-dihydroquinoline-2,4'-piperidine]-1'-carboxamide Chemical compound N[C@@H](C(F)(F)F)C=1C=C(CNC(=O)N2CCC3(N(C4=CC=C(C=C4C(C3)O)F)C)CC2)C=CC=1F OSUAIFHDIUGTQU-BPGUCPLFSA-N 0.000 claims 1
- 108010071382 NF-E2-Related Factor 2 Proteins 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 108010065942 Prostaglandin-F synthase Proteins 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 208000009956 adenocarcinoma Diseases 0.000 claims 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229910052805 deuterium Inorganic materials 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 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
- 230000004076 epigenetic alteration Effects 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 230000014509 gene expression Effects 0.000 claims 1
- 230000004077 genetic alteration Effects 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 208000014212 sarcomatoid carcinoma Diseases 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 230000002103 transcriptional effect Effects 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4747—Quinolines; Isoquinolines spiro-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (15)
1. Spoj, naznačen time, što je predstavljen formulom (I):
[image]
ili njegova farmaceutski prihvatljiva sol,
u kojoj:
- - - - - je jednostruka veza ili dvostruka veza;
Z je ili OH, kada - - - - - - je jednostruka veza; ili O, kada - - - - - - je dvostruka veza;
svaki R1 je neovisno odabran iz skupine koja sadrži (C1-C6)alkil, (C1-C6)alkoksi, (C0-C4)alkilN(R8)2, i halogen;
R2a i R2b su svaki neovisno odabrani iz skupine koja sadrži H, (C1-C6) alkil, i halogen;
svaki R3 je neovisno odabran iz skupine koja sadrži H, i halogen;
R4 je odabran iz skupine koja sadrži aril, 5 do 6-člani heteroaril koji sadrži 1, 2, 3, ili 4 heteroatoma neovisno odabrana između N, O, i S; i 9 do 10-člani kondenzirani biciklički heteroaril koji sadrži 1, 2, 3, ili 4 heteroatoma neovisno odabrana između N, O, i S; pri čemu je bilo koji od pretodno navedenih izborno supstituiran s jednim ili više R6;
R5 je odabran iz skupine koja sadrži H; (C1-C6)alkil; (C2-C6)alkenil; (C0-C4)alkilOR8; (C1-C4)alkil(C3-C10)cikloalkil; halo(C1-C6)alkil; (C2-C3)alkinil; (C1-C4)alkilN(R10)2;
svaki R6 je neovisno odabran iz skupine koja sadrži halogen; (C1-C6)alkil; (C1-C6)alkoksi; halo(C1-C6)alkil; OH; aril; 3 do 6-člani heterocikl; 5 do 6-člani heteroaril; (C0-C4 )alkilS(O)m(C1-C6)alkil; halo(C1-C6)alkoksi; (C0-C4)alkilS(O)mN(R8)2; (C0-C4)alkil N(R8)2; (C0-C4)alkil(CO)OR7; N(R8)S(O)m(C1-C6)alkil; N(R8)S(O)m(C3-C6)cikloalkil; OP(O)(OH)2; (C0-C3)alkil(CO)NHR11; (C0-C3)alkilOR7, i (C3-C10)cikloalkil; pri čemu svaki R6, kada nije halogen, OH, ili OP(O)(OH)2, je izborno supstituiran s jednim do tri R9; ili dva susjedna R6, zajedno s atomima za koje se oni vežu, tvore 5 do 7-člani heterocikl ili (C5-C8)cikloalkil;
svaki R7 i R8 je neovisno odabran iz skupine koja sadrži H ili (C1-C6)alkil, koji je izborno supstituiran s jednim do tri R9;
svaki R9 je neovisno odabran iz skupine koja sadrži halogen; -OH; amino, (C1-C4)alkilamino, di(C1-C4)alkilamino, OP(O)(OH)2 ;(C1-C6)alkil; (C1-C3)alkinil; (C1-C6)alkoksi; halo(C1-C6)alkil; (C0-C4)alkilS(O)m(C1-C6)alkil; halo(C1-C6)alkoksi; 3 do 6-člani heterocikl koji je po izboru supstituiran s okso (=O); (C0-C4)alkilS(O)mN(R10)2; (C0-C4)alkil(CO)R10; (C0-C4)alkil(CO)OR10; (C0-C4)alkilNR10S(O)m(C1-C6)alkil; (C0-C4)alkilOR10; (C0-C4)alkilN(R10)2; (C0-C4)alkilCN; (C0-C4)alkilN(R10)2; i (C0-C4)alkil(CO)N(R10)2;
svaki R10 je neovisno odabran iz skupine koja sadrži H, (C1-C6)alkil; ili 3 do 6-člani heterocikl, pri čemu je 3 do 6-člani heterocikl izborno supstituiran s jednim ili više (C1-C6)alkil; i okso (=O);
svaki R11 je odabran iz skupine koja sadrži H; 4 do 6-člani heterocikl koji je po izboru supstituiran s jednim do četiri R12; (C3-C6)cikloalkil koji je po izboru supstituiran s jednim do četiri R12; (C0-C3)alkil(C3-C6)cikloalkil (C1-C3)alkil koji je po izboru supstituiran s halogenom; CH2-aril koji je izborno supstituiran s jednim do tri R12; (C1-C6)alkil; (C2-C6)alkenil; ili (C2-C6)alkinil, pri čemu svaki od (C1-C6)alkil; (C2-C6)alkenil; i (C2-C6)alkinil je izborno supstituiran s jednim ili više R13;
svaki R12 je neovisno odabran iz skupine koja sadrži OH, (C1-C3)alkoksi, NH2; ili (C1-C3)alkil izborno supstituiran s jednim ili više OH;
svaki R13 je neovisno odabran iz skupine koja sadrži halogen, OH, amino, (C1-C4)alkilamino, di(C1-C4)alkilamino, (C1-C3)alkoksi; i C(O)-(C3-C8)cikloalkil;
m je 0, 1, ili 2; i
n je 0, 1 ili 2.
2. Spoj prema patentnom zahtjevu 1, naznačen time, što je R4:
a) fenil izborno supstituiran s jednim ili više R6, ili
b) 5 do 6-člani heteroaril izborno supstituiran s jednim ili više R6 (npr. gdje R4 je piridil, ili pri čemu je R4 odabran iz skupine koja sadrži furil, oksazolil, pirazolil, izoksazolil, tiofenil, imidazolil, i oksadiazolil).
3. Spoj prema patentnom zahtjevu 2, naznačen time, što ima formulu (II),
[image]
ili njegova farmaceutski prihvatljiva sol.
4. Spoj prema patentnom zahtjevu 1, naznačen time, što ima formulu (III),
[image]
ili njegova farmaceutski prihvatljiva sol,
pri čemu prsten A je 5-člani heteroaril i
u, v, w, i x su svaki neovisno odabrani iz skupine CH, O, S, N, i NH, pod uvjetom da najmanje jedan od u, v, w, i x je O, S, N ili NH.
5. Spoj prema bilo kojem od patentnih zahtjeva 1, 2 ili 4,
naznačen time, što n je 1 ili 2; i
R4 je
[image]
[image]
pri čemu R4 je izborno supstituiran s jednim do tri R6.
6. Spoj prema bilo kojem od patentnih zahtjeva 1-5, naznačen time, što n je 1 ili 2, i: a) najmanje jedan R1 je halogen, i/ili b) najmanje jedan R1 je F.
7. Spoj prema bilo kojem od patentnih zahtjeva 1-6, naznačen time, što n je 1, i/ili Z je O.
8. Spoj prema bilo kojem od patentnih zahtjeva 1-7, naznačen time, što R2a i R2b su svaki H.
9. Spoj prema bilo kojem od patentnih zahtjeva 1-8, naznačen time, što R5 je H; (C1-C6)alkil; (C2-C6)alkenil; ili (C0-C4)alkilOR8, npr. gdje R5 je H ili (C1-C2)alkil, npr. gdje R5 je H.
10. Spoj prema bilo kojem od patentnih zahtjeva 1-9, naznačen time, što je svaki R3 H, npr. gdje svaki R3 je deuterij.
11. Spoj prema bilo kojem od patentnih zahtjeva 1-10, naznačen time, što je svaki R6 neovisno odabran između halogena i (C0-C4)alkilN(R8)2, npr. gdje R6 je halogen.
12. Spoj prema patentnom zahtjevu 1, naznačen time, što je spoj odabran iz niza koji čine:
6'-fluor-N-((5-metilfuran-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-metoksibenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksietoksi)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
4-((6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil dihidrogen fosfat;
N-(2,4-difluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
1'-etil-6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-1'-metil-N-((5-metilfuran-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-metoksibenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((2-metilfuran-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbe;nzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid
6'-fluor-N-((4-fluorfenil)metil-d2)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-(2-metoksietil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(oksazol-5-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-(2-hidroksietil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-((2-metoksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((5-klorfuran-2-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((1-metiletil)sulfonamido)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
1'-etil-6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
2-((2-fluor-5-((6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil)amino)etil dihidrogen fosfat;
N-(3-amino-4-fluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-sulfamoilbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(((1,4-dioksan-2-il)metil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((4-(hidroksimetil)benzil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-benzil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((2,4-dimetilfuran-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(3-(oksazol-5-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-pirazol-4-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((4-karbamoilfuran-2-il)metil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2,2-dimetil-3-(4-metilpiperazin-1-il)-3-oksopropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-N-(3-((2,3-dihidroksipropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(furan-3-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-pirazol-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,5-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(5-amino-2,4-difluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-(2,2,2-trifluoretoksi)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-(etilamino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(benzo[d][1,3]dioksol-4-ilmetil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(4-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilsulfonamido)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,3-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((2-metilfuran-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((3-hidroksiciklobutil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
metil 2-fluor-5-((6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)benzoat;
N-(3-(2-amino-2-oksoetil)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((3-hidroksipiridin-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3,5-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((6-(dimetilamino)piridin-2-il)metil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-(trifluormetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-klor-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksietoksi)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-(2-hidroksietoksi)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((5-metil-1H-pirazol-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-4'-okso-N-(3-sulfamoilbenzil)-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-3-((2-hidroksietil)amino)benzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-aminobenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluor-2-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,6-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2-(dimetilamino)etil)karbamoil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(E)-1'-(but-2-en-1-il)-6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-((2-hidroksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-klorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-aminobenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-(2-oksopirolidin-1-il)etil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-3-((2-hidroksietil)amino)benzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(1-hidroksietil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((4-klor-1-metil-1H-pirazol-5-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-4'-okso-N-((2-(trifluormetil)furan-3-il)metil)-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksi-2-metilpropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2-ciklopropil-2-oksoetil)karbamoil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2,2,2-trifluoretil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(3-metoksiazetidin-1-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(2-amino-2-oksoetil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-(trifluormetil)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(oksetan-3-ilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((3-etil-5-metilizoksazol-4-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-4-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-(difluormetoksi)-3-fluorbenzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((2,5-dimetilfuran-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-klorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-(trifluormetil)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2,2-dimetil-3-morfolino-3-oksopropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-metoksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((2-metoksipiridin-4-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-3-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-indol-6-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(((2-metiloksazol-5-il)metil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(E)-6'-fluor-N-(4-fluor-3-((4-hidroksibut-2-en-1-il)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((5-metiltiofen-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-5-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((6-fluorpiridin-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(5-amino-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((5-metil-2-(trifluormetil)furan-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(prop-2-in-1-ilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(1H-imidazol-2-il)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilsulfonamido)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(4-fluor-3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(ciklopropansulfonamido)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((3-metil-1,2,4-oksadiazol-5-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(1-hidroksietil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((6-aminopiridin-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-amino-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(oksazol-4-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksipropan-2-il)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
3-((2-fluor-5-((6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil)amino)-2,2-dimetilpropanska kiselina;
N-(benzo[c][1,2,5]oksadiazol-4-ilmetil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-8'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(propilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(1H-1,2,4-triazol-1-il)benzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((1-metil-1H-pirazol-4-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(((2-hidroksietil)amino)metil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(sulfamoilmetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
3-((2-fluor-5-((6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil)amino)propanska kiselina;
(R)-N-(3-(1-amino-2,2,2-trifluoretil)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-(difluormetoksi)benzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-N-(4-fluorbenzil)-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-6'-fluor-N-(4-fluorbenzil)-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-N-(4-fluorbenzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-6'-fluor-N-(4-fluorbenzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-N-(4-fluor-2-hidroksibenzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-6'-fluor-N-(4-fluor-2-hidroksibenzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-6'-fluor-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6',8'-difluor-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6'-fluor-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(hidroksimetil)benzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(2-amino-2-oksoetil)-4-fluorbenzil)-6'-fluor-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((3-hidroksiciklobutil)karbamoil)benzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksietoksi)benzil)-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilsulfonamido)benzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-((2-metoksietil)amino)benzil)-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((R)-1-amino-2,2,2-trifluoretil)-4-fluorbenzil)-6'-fluor-4'-hidroksi-1'-metil-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-metoksibenzil)-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-4'-hidroksi-N-((2-metilfuran-3-il)metil)-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-N-(4-amino-3-fluorbenzil)-6'-fluor-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid; i
(S)-N-(4-amino-3-fluorbenzil)-6'-fluor-4'-hidroksi-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
ili njihova farmaceutski prihvatljiva sol,
npr. a) pri čemu je spoj odabran iz niza koji sadrži:
6'-fluor-N-(4-fluor-2-metoksibenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksietoksi)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
4-((6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil dihidrogen fosfat;
N-(2,4-difluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
1'-etil-6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-metoksibenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((4-fluorfenil)metil-d2)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-(2-metoksietil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(oksazol-5-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-1'-(2-hidroksietil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-((2-metoksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((1-metiletil)sulfonamido)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
1'-etil-6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
2-((2-fluor-5-((6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil)amino)etil dihidrogen fosfat;
N-(3-amino-4-fluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-sulfamoilbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(((1,4-dioksan-2-il)metil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((4-(hidroksimetil)benzil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-benzil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(3-(oksazol-5-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2,2-dimetil-3-(4-metilpiperazin-1-il)-3-oksopropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-N-(3-((2,3-dihidroksipropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,5-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(5-amino-2,4-difluorbenzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-(2,2,2-trifluoretoksi)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-(etilamino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(benzo[d][1,3]dioksol-4-ilmetil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(4-hidroksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilsulfonamido)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,3-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((3-hidroksiciklobutil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
metil 2-fluor-5-((6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)benzoat;
N-(3-(2-amino-2-oksoetil)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3,5-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-(trifluormetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-klor-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksietoksi)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-(2-hidroksietoksi)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-4'-okso-N-(3-sulfamoilbenzil)-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-3-((2-hidroksietil)amino)benzil)-1'-etil-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-aminobenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-5-((2-hidroksietil)amino)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-4-fluor-2-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2,6-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2-(dimetilamino)etil)karbamoil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksietil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid:
(E)-1'-(but-2-en-1-il)-6'-fluor-N-(4-fluorbenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-((2-hidroksietil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-klorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-aminobenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-(2-oksopirolidin-1-il)etil)amino)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2,4-difluor-3-((2-hidroksietil)amino)benzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(1-hidroksietil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-amino-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-hidroksi-2-metilpropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2-metoksietil)amino)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2-ciklopropil-2-oksoetil)karbamoil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-((2,2,2-trifluoretil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(3-metoksiazetidin-1-il)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(2-amino-2-oksoetil)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-(trifluormetil)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(oksetan-3-ilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-(difluormetoksi)-3-fluorbenzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-karbamoil-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-klorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-(trifluormetil)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-((2,2-dimetil-3-morfolino-3-oksopropil)amino)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-2-metoksibenzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-2-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(S)-6'-fluor-N-(4-fluor-3-((2-hidroksipropil)karbamoil)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(4-amino-3-metilbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(((2-metiloksazol-5-il)metil)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(E)-6'-fluor-N-(4-fluor-3-((4-hidroksibut-2-en-1-il)karbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(5-amino-2,4-difluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(prop-2-in-1-ilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(1H-imidazol-2-il)benzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(metilsulfonamido)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(4-fluor-3-(hidroksimetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(ciklopropansulfonamido)-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(1-hidroksietil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(2-amino-4-fluorbenzil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(2-hidroksipropan-2-il)benzil)-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
3-((2-fluor-5-((6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamido)metil)fenil)amino)-2,2-dimetilpropanska kiselina;
N-(3-karbamoil-4-fluorbenzil)-6'-fluor-8'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(propilkarbamoil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(3-(1H-1,2,4-triazol-1-il)benzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(((2-hidroksietil)amino)metil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(4-fluor-3-(sulfamoilmetil)benzil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
(R)-N-(3-(1-amino-2,2,2-trifluoretil)-4-fluorbenzil)-6'-fluor-1'-metil-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid; i
N-(4-(difluormetoksi)benzil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
ili njihova farmaceutski prihvatljiva sol,
ili b) pri čemu je spoj odabran iz niza koji sadrži:
6'-fluor-N-((5-metilfuran-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-1'-metil-N-((5-metilfuran-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((2-metilfuran-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((5-klorfuran-2-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((2,4-dimetilfuran-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-pirazol-4-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((4-karbamoilfuran-2-il)metil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-(furan-3-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-pirazol-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((2-metilfuran-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((3-hidroksipiridin-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((6-(dimetilamino)piridin-2-il)metil)-6',8'-difluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((5-metil-1H-pirazol-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((4-klor-1-metil-1H-pirazol-5-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-4'-okso-N-((2-(trifluormetil)furan-3-il)metil)-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((3-etil-5-metilizoksazol-4-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-4-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((2,5-dimetilfuran-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((2-metoksipiridin-4-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-3-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((1H-indol-6-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((5-metiltiofen-2-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(izoksazol-5-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6',8'-difluor-N-((6-fluorpiridin-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((5-metil-2-(trifluormetil)furan-3-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-((3-metil-1,2,4-oksadiazol-5-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-((6-aminopiridin-3-il)metil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
6'-fluor-N-(oksazol-4-ilmetil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
N-(benzo[c][1,2,5]oksadiazol-4-ilmetil)-6'-fluor-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid; i
6'-fluor-N-((1-metil-1H-pirazol-4-il)metil)-4'-okso-3',4'-dihidro-1'H-spiro[piperidin-4,2'-kinolin]-1-karboksamid;
ili njihova farmaceutski prihvatljiva sol.
13. Farmaceutski pripravak, naznačen time, što sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 12, i jedan ili više farmaceutski prihvatljivih nosača.
14. Farmaceutska kombinacija, naznačena time, što sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 12, ili njegovu farmaceutski prihvatljivu sol, i jedno ili više terapijskih sredstava.
15. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, naznačen time, što se koristi kao lijek, npr. za liječenje ili prevenciju bolesti ili stanja posredovanih KARS-om, kao što je rak, npr. pri čemu je rak odabran od raka pluća nemalih stanica (NSCLC), raka jetre, raka glave i vrata, raka jednjaka, raka maternice, raka dojke, raka mokraćnog mjehura, raka grlića maternice, kolorektalnog raka, raka bubrega, melanoma, raka želuca, raka prostate otpornog na kastraciju (CRPC), T-stanične akutne limfoblastične leukemije (T-ALL), akutne mijeloične leukemije (AML), i mijelodisplastičnog sindroma (MDS), npr. pri čemu je karcinom pluća nemalih stanica (NSCLC) odabran od adenokarcinoma, karcinoma pločastih stanica, karcinoma velikih stanica, neuroendokrinog karcinoma velikih stanica, adenoskvamoznog karcinoma, i sarkomatoidnog karcinoma, npr. pri čemu rak ima genetsku ili epigenetsku promjenu u genima NFE2L2, KEAP1, CUL3, AKR1C3 ili bilo koje drugo stanje koje rezultira aktivacijom transkripcijske aktivnosti NRF2 ili ekspresije gena AKR1C3.
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| WO2022048492A1 (zh) | 2020-09-02 | 2022-03-10 | 深圳艾欣达伟医药科技有限公司 | 一种akr1c3检测方法、检测akr1c3的诊断试剂盒及其用途 |
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| US20100048604A1 (en) * | 2004-08-20 | 2010-02-25 | Yee Dominic J | Ligands for Aldoketoreductases |
| US8110578B2 (en) | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| EP3078374B1 (en) * | 2011-10-17 | 2019-06-19 | Vanderbilt University | Indomethacin analogs for the treatment of castrate-resistant prostate cancer |
| MY192888A (en) | 2015-03-10 | 2022-09-14 | Ascentawits Pharmaceuticals Ltd | Dna alkylating agents |
| US10167293B2 (en) * | 2016-05-26 | 2019-01-01 | Bayer Pharma Aktiengesellschaft | [8-(phenylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanones |
| UY38806A (es) | 2019-08-01 | 2021-02-26 | Novartis Ag | Compuestos inhibidores tricíclicos de kars dependientes de akr1c3, composiciones y sus usos |
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