HRP20201396T1 - Tetrahidro-pirido[3,4-b]indoli kao modulatori estrogenih receptora i njihove primjene - Google Patents
Tetrahidro-pirido[3,4-b]indoli kao modulatori estrogenih receptora i njihove primjene Download PDFInfo
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- HRP20201396T1 HRP20201396T1 HRP20201396TT HRP20201396T HRP20201396T1 HR P20201396 T1 HRP20201396 T1 HR P20201396T1 HR P20201396T T HRP20201396T T HR P20201396TT HR P20201396 T HRP20201396 T HR P20201396T HR P20201396 T1 HRP20201396 T1 HR P20201396T1
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- Prior art keywords
- methyl
- fluoropropyl
- azetidin
- indol
- fluoro
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- CFTOTSJVQRFXOF-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CNCC2 CFTOTSJVQRFXOF-UHFFFAOYSA-N 0.000 title 1
- 239000002834 estrogen receptor modulator Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 37
- -1 1-methylazetidin-3-yl Chemical group 0.000 claims 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 11
- 206010006187 Breast cancer Diseases 0.000 claims 10
- 208000026310 Breast neoplasm Diseases 0.000 claims 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 8
- 229910052794 bromium Inorganic materials 0.000 claims 7
- 229910052801 chlorine Inorganic materials 0.000 claims 7
- 229910052731 fluorine Inorganic materials 0.000 claims 7
- 229910052740 iodine Inorganic materials 0.000 claims 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
- 125000000623 heterocyclic group Chemical group 0.000 claims 5
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 4
- GQCXHIKRWBIQMD-AKJBCIBTSA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)CC(CO)(F)F GQCXHIKRWBIQMD-AKJBCIBTSA-N 0.000 claims 4
- IHPLYTHECYNRBF-PVPMGCCUSA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=C(C=C21)F)C)CC(CO)(F)F IHPLYTHECYNRBF-PVPMGCCUSA-N 0.000 claims 4
- 125000002393 azetidinyl group Chemical group 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 4
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims 4
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 4
- 125000003566 oxetanyl group Chemical group 0.000 claims 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 2
- 229940124297 CDK 4/6 inhibitor Drugs 0.000 claims 2
- NQLMGOWDIRVRGW-SGANQWHYSA-N N-[3,5-difluoro-4-[(1R,3R)-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)CC(F)(F)F)F)NC1CN(C1)CCCF NQLMGOWDIRVRGW-SGANQWHYSA-N 0.000 claims 2
- ZARAMMLYSFBVHU-DLUDVSRJSA-N N-[3,5-difluoro-4-[(1R,3R)-7-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC(=CC=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF ZARAMMLYSFBVHU-DLUDVSRJSA-N 0.000 claims 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims 2
- 230000003388 anti-hormonal effect Effects 0.000 claims 2
- 239000003886 aromatase inhibitor Substances 0.000 claims 2
- 229940046844 aromatase inhibitors Drugs 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 230000001419 dependent effect Effects 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 230000003637 steroidlike Effects 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- GLBLQKSZHVJLTN-IGOFHWAASA-N (2R)-2-[[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]methyl]-2-fluoro-3-hydroxypropanenitrile Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)C[C@@](C#N)(CO)F GLBLQKSZHVJLTN-IGOFHWAASA-N 0.000 claims 1
- KFTAJRYKGSJCGH-WMEVLASGSA-N (2R)-2-fluoro-3-[(1R,3R)-1-[2-fluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropan-1-ol Chemical compound F[C@@](CO)(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C1=C(C=C(C=C1)NC1CN(C1)CCCF)F)C KFTAJRYKGSJCGH-WMEVLASGSA-N 0.000 claims 1
- FTNSQRCBGLNFNE-OYZWHMGFSA-N (2R)-2-fluoro-3-[(1R,3R)-1-[4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropan-1-ol Chemical compound C[C@@H]1CC2=C(NC3=CC=CC=C23)[C@H](N1C[C@@](C)(F)CO)C1=CC=C(NC2CN(CCCF)C2)C=C1 FTNSQRCBGLNFNE-OYZWHMGFSA-N 0.000 claims 1
- RYMNYVCYDCNHCQ-SGNOPVRASA-N (2R)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound C[C@@H]1CC2=C(NC3=CC=CC=C23)[C@H](N1C[C@@](C)(F)CO)C1=C(F)C=C(NC2CN(CCCF)C2)C=C1F RYMNYVCYDCNHCQ-SGNOPVRASA-N 0.000 claims 1
- FVUFWUCRFHWDBG-DDWQGHIRSA-N (2R)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropanoic acid Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)C[C@H](C(=O)O)C FVUFWUCRFHWDBG-DDWQGHIRSA-N 0.000 claims 1
- BFWRDQNWWDCNSE-XBJZADGRSA-N (2R)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC(=C21)F)C)C[C@@](CO)(C)F BFWRDQNWWDCNSE-XBJZADGRSA-N 0.000 claims 1
- YXVDVAQFLJVHLP-XBJZADGRSA-N (2R)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC(=CC=C21)F)C)C[C@@](CO)(C)F YXVDVAQFLJVHLP-XBJZADGRSA-N 0.000 claims 1
- XICGBKVMLCHTHV-CKZDFEDFSA-N (2R)-3-[(1R,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@H](CC2=C1NC1=CC=C(C=C21)F)C)C[C@@](CO)(C)F XICGBKVMLCHTHV-CKZDFEDFSA-N 0.000 claims 1
- BFWRDQNWWDCNSE-ATHLUOJYSA-N (2R)-3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC=CC(=C21)F)C)C[C@@](CO)(C)F BFWRDQNWWDCNSE-ATHLUOJYSA-N 0.000 claims 1
- YXVDVAQFLJVHLP-ATHLUOJYSA-N (2R)-3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC(=CC=C21)F)C)C[C@@](CO)(C)F YXVDVAQFLJVHLP-ATHLUOJYSA-N 0.000 claims 1
- GLBLQKSZHVJLTN-SGNOPVRASA-N (2S)-2-[[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]methyl]-2-fluoro-3-hydroxypropanenitrile Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)C[C@](C#N)(CO)F GLBLQKSZHVJLTN-SGNOPVRASA-N 0.000 claims 1
- KFTAJRYKGSJCGH-RKGKASADSA-N (2S)-2-fluoro-3-[(1R,3R)-1-[2-fluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropan-1-ol Chemical compound C[C@@H]1Cc2c([nH]c3ccccc23)[C@H](N1C[C@](C)(F)CO)c1ccc(NC2CN(CCCF)C2)cc1F KFTAJRYKGSJCGH-RKGKASADSA-N 0.000 claims 1
- FTNSQRCBGLNFNE-LHXLBICKSA-N (2S)-2-fluoro-3-[(1R,3R)-1-[4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropan-1-ol Chemical compound F[C@](CO)(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C1=CC=C(C=C1)NC1CN(C1)CCCF)C FTNSQRCBGLNFNE-LHXLBICKSA-N 0.000 claims 1
- RYMNYVCYDCNHCQ-IGOFHWAASA-N (2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound C[C@@H]1CC2=C(NC3=CC=CC=C23)[C@H](N1C[C@](C)(F)CO)C1=C(F)C=C(NC2CN(CCCF)C2)C=C1F RYMNYVCYDCNHCQ-IGOFHWAASA-N 0.000 claims 1
- FVUFWUCRFHWDBG-ANAQZDLVSA-N (2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-methylpropanoic acid Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)C[C@@H](C(=O)O)C FVUFWUCRFHWDBG-ANAQZDLVSA-N 0.000 claims 1
- BFWRDQNWWDCNSE-JOLLRLPSSA-N (2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC(=C21)F)C)C[C@](CO)(C)F BFWRDQNWWDCNSE-JOLLRLPSSA-N 0.000 claims 1
- XICGBKVMLCHTHV-JOLLRLPSSA-N (2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=C(C=C21)F)C)C[C@](CO)(C)F XICGBKVMLCHTHV-JOLLRLPSSA-N 0.000 claims 1
- YXVDVAQFLJVHLP-JOLLRLPSSA-N (2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC(=CC=C21)F)C)C[C@](CO)(C)F YXVDVAQFLJVHLP-JOLLRLPSSA-N 0.000 claims 1
- BFWRDQNWWDCNSE-YLTFJWLSSA-N (2S)-3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC=CC(=C21)F)C)C[C@](CO)(C)F BFWRDQNWWDCNSE-YLTFJWLSSA-N 0.000 claims 1
- XICGBKVMLCHTHV-YLTFJWLSSA-N (2S)-3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC=C(C=C21)F)C)C[C@](CO)(C)F XICGBKVMLCHTHV-YLTFJWLSSA-N 0.000 claims 1
- YXVDVAQFLJVHLP-YLTFJWLSSA-N (2S)-3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2-fluoro-2-methylpropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC(=CC=C21)F)C)C[C@](CO)(C)F YXVDVAQFLJVHLP-YLTFJWLSSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 1
- UEHVNZOVIHETBF-CRICUBBOSA-N 1-(3-fluoropropyl)-N-[4-[(1R,3R)-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]azetidin-3-amine Chemical compound FCCCN1CC(C1)NC1=CC=C(C=C1)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)S(=O)(=O)C UEHVNZOVIHETBF-CRICUBBOSA-N 0.000 claims 1
- UEHVNZOVIHETBF-NSYGIPOTSA-N 1-(3-fluoropropyl)-N-[4-[(1S,3R)-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]azetidin-3-amine Chemical compound FCCCN1CC(C1)NC1=CC=C(C=C1)[C@@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)S(=O)(=O)C UEHVNZOVIHETBF-NSYGIPOTSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- FUCGJBBZOPTUQB-AREMUKBSSA-N 3-[(1R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3,3-dimethyl-4,9-dihydro-1H-pyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N(C(CC2=C1NC1=CC=CC=C21)(C)C)CC(CO)(F)F FUCGJBBZOPTUQB-AREMUKBSSA-N 0.000 claims 1
- CXSKAGRTYNHVTD-XGCWNURASA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-dimethylpropanoic acid Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)CC(C(=O)O)(C)C CXSKAGRTYNHVTD-XGCWNURASA-N 0.000 claims 1
- CQQRFPSWPGCKCH-PVPMGCCUSA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC=CC(=C21)F)C)CC(CO)(F)F CQQRFPSWPGCKCH-PVPMGCCUSA-N 0.000 claims 1
- NESQDZKUKHWOLS-PVPMGCCUSA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=CC(=CC=C21)F)C)CC(CO)(F)F NESQDZKUKHWOLS-PVPMGCCUSA-N 0.000 claims 1
- DGCYBRDAKZFTDA-PVPMGCCUSA-N 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-8-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@H]1N([C@@H](CC2=C1NC1=C(C=CC=C21)F)C)CC(CO)(F)F DGCYBRDAKZFTDA-PVPMGCCUSA-N 0.000 claims 1
- FUCGJBBZOPTUQB-SANMLTNESA-N 3-[(1S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3,3-dimethyl-4,9-dihydro-1H-pyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N(C(CC2=C1NC1=CC=CC=C21)(C)C)CC(CO)(F)F FUCGJBBZOPTUQB-SANMLTNESA-N 0.000 claims 1
- CQQRFPSWPGCKCH-HAWMADMCSA-N 3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-5-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC=CC(=C21)F)C)CC(CO)(F)F CQQRFPSWPGCKCH-HAWMADMCSA-N 0.000 claims 1
- IHPLYTHECYNRBF-HAWMADMCSA-N 3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC=2C3=CC(=CC=C3NC1=2)F)C)CC(CO)(F)F IHPLYTHECYNRBF-HAWMADMCSA-N 0.000 claims 1
- NESQDZKUKHWOLS-HAWMADMCSA-N 3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-7-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound FC1=C(C(=CC(=C1)NC1CN(C1)CCCF)F)[C@@H]1N([C@H](CC2=C1NC1=CC(=CC=C21)F)C)CC(CO)(F)F NESQDZKUKHWOLS-HAWMADMCSA-N 0.000 claims 1
- DGCYBRDAKZFTDA-HAWMADMCSA-N 3-[(1S,3S)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-8-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol Chemical compound C[C@H]1CC2=C(NC3=C2C=CC=C3F)[C@@H](N1CC(F)(F)CO)C1=C(F)C=C(NC2CN(CCCF)C2)C=C1F DGCYBRDAKZFTDA-HAWMADMCSA-N 0.000 claims 1
- RHXHGRAEPCAFML-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 RHXHGRAEPCAFML-UHFFFAOYSA-N 0.000 claims 1
- 206010055113 Breast cancer metastatic Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- IXSLWFRMFRUPOZ-KWMCUTETSA-N N-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)-N-methylazetidin-3-amine Chemical compound C[C@@H]1CC2=C(NC3=CC=CC=C23)[C@H](N1CC(C)(C)F)C1=C(F)C=C(C=C1F)N(C)C1CN(CCCF)C1 IXSLWFRMFRUPOZ-KWMCUTETSA-N 0.000 claims 1
- HIDXTQSBUYNMBC-XGCWNURASA-N N-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)CC(C)(C)F)F)NC1CN(C1)CCCF HIDXTQSBUYNMBC-XGCWNURASA-N 0.000 claims 1
- XDPCOGVSOVRXGB-SGANQWHYSA-N N-[3,5-difluoro-4-[(1R,3R)-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)S(=O)(=O)C)F)NC1CN(C1)CCCF XDPCOGVSOVRXGB-SGANQWHYSA-N 0.000 claims 1
- XASXPVMDAFGBOH-DLUDVSRJSA-N N-[3,5-difluoro-4-[(1R,3R)-5-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=CC(=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF XASXPVMDAFGBOH-DLUDVSRJSA-N 0.000 claims 1
- KLFNOQSSTYUNPB-DLUDVSRJSA-N N-[3,5-difluoro-4-[(1R,3R)-6-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=C(C=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF KLFNOQSSTYUNPB-DLUDVSRJSA-N 0.000 claims 1
- MZYTYOWREFKNDQ-DLUDVSRJSA-N N-[3,5-difluoro-4-[(1R,3R)-6-fluoro-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=CC=C(C=C21)F)C)S(=O)(=O)C)F)NC1CN(C1)CCCF MZYTYOWREFKNDQ-DLUDVSRJSA-N 0.000 claims 1
- YKIQKXYDDXCUPR-DLUDVSRJSA-N N-[3,5-difluoro-4-[(1R,3R)-8-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@H]1N([C@@H](CC2=C1NC1=C(C=CC=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF YKIQKXYDDXCUPR-DLUDVSRJSA-N 0.000 claims 1
- XDPCOGVSOVRXGB-BZQUYTCOSA-N N-[3,5-difluoro-4-[(1S,3R)-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@@H](CC2=C1NC1=CC=CC=C21)C)S(=O)(=O)C)F)NC1CN(C1)CCCF XDPCOGVSOVRXGB-BZQUYTCOSA-N 0.000 claims 1
- XASXPVMDAFGBOH-SXBQZSJRSA-N N-[3,5-difluoro-4-[(1S,3S)-5-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@H](CC2=C1NC1=CC=CC(=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF XASXPVMDAFGBOH-SXBQZSJRSA-N 0.000 claims 1
- KLFNOQSSTYUNPB-SXBQZSJRSA-N N-[3,5-difluoro-4-[(1S,3S)-6-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@H](CC2=C1NC1=CC=C(C=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF KLFNOQSSTYUNPB-SXBQZSJRSA-N 0.000 claims 1
- MZYTYOWREFKNDQ-SXBQZSJRSA-N N-[3,5-difluoro-4-[(1S,3S)-6-fluoro-3-methyl-2-methylsulfonyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@H](CC2=C1NC1=CC=C(C=C21)F)C)S(=O)(=O)C)F)NC1CN(C1)CCCF MZYTYOWREFKNDQ-SXBQZSJRSA-N 0.000 claims 1
- ZARAMMLYSFBVHU-SXBQZSJRSA-N N-[3,5-difluoro-4-[(1S,3S)-7-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@H](CC2=C1NC1=CC(=CC=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF ZARAMMLYSFBVHU-SXBQZSJRSA-N 0.000 claims 1
- YKIQKXYDDXCUPR-SXBQZSJRSA-N N-[3,5-difluoro-4-[(1S,3S)-8-fluoro-3-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC=1C=C(C=C(C=1[C@@H]1N([C@H](CC2=C1NC1=C(C=CC=C21)F)C)CC(F)(F)F)F)NC1CN(C1)CCCF YKIQKXYDDXCUPR-SXBQZSJRSA-N 0.000 claims 1
- IGKRPAKADHIFRZ-AREMUKBSSA-N N-[4-[(1R)-2-(2,2-difluoroethyl)-3,3-dimethyl-4,9-dihydro-1H-pyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2CC1(C)C)C1=C(C=C(C=C1F)NC1CN(C1)CCCF)F)F IGKRPAKADHIFRZ-AREMUKBSSA-N 0.000 claims 1
- DVZRNWXCWBKUMR-PVPMGCCUSA-N N-[4-[(1R,3R)-2-(2,2-difluoroethyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C1=C(C=C(C=C1F)NC1CN(C1)CCCF)F)F DVZRNWXCWBKUMR-PVPMGCCUSA-N 0.000 claims 1
- HUOAOMHWMJLCSA-IYJVBRSBSA-N N-[4-[(1R,3R)-2-(2,2-difluoroethyl)-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC(CN1[C@@H](C=2NC3=CC=C(C=C3C=2C[C@H]1C)F)C1=C(C=C(C=C1F)NC1CN(C1)CCCF)F)F HUOAOMHWMJLCSA-IYJVBRSBSA-N 0.000 claims 1
- IGKRPAKADHIFRZ-SANMLTNESA-N N-[4-[(1S)-2-(2,2-difluoroethyl)-3,3-dimethyl-4,9-dihydro-1H-pyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC(CN1[C@H](C=2NC3=CC=CC=C3C=2CC1(C)C)C1=C(C=C(C=C1F)NC1CN(C1)CCCF)F)F IGKRPAKADHIFRZ-SANMLTNESA-N 0.000 claims 1
- HUOAOMHWMJLCSA-RXBISOJRSA-N N-[4-[(1S,3S)-2-(2,2-difluoroethyl)-6-fluoro-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]-3,5-difluorophenyl]-1-(3-fluoropropyl)azetidin-3-amine Chemical compound FC(CN1[C@H](C=2NC3=CC=C(C=C3C=2C[C@@H]1C)F)C1=C(C=C(C=C1F)NC1CN(C1)CCCF)F)F HUOAOMHWMJLCSA-RXBISOJRSA-N 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
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- 102000015694 estrogen receptors Human genes 0.000 claims 1
- 108010038795 estrogen receptors Proteins 0.000 claims 1
- 229960002258 fulvestrant Drugs 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 108091008039 hormone receptors Proteins 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 229960004390 palbociclib Drugs 0.000 claims 1
- AHJRHEGDXFFMBM-UHFFFAOYSA-N palbociclib Chemical group N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 AHJRHEGDXFFMBM-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229950003687 ribociclib Drugs 0.000 claims 1
- 229960001603 tamoxifen Drugs 0.000 claims 1
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Classifications
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
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- 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
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- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Claims (28)
1. Spoj, naznačen time, da je odabran iz formule Ih:
[image]
ili stereoizomera, tautomera ili njihovih farmaceutski prihvatljivih soli, pri čemu:
Y2 je −(CH2)-;
Ra je odabran od: H, C1-C6 alkil, C2-C8 alkenil, propargil, C3-C6 cikloalkil i C3-C6 heterociklil, opcijski supstituiran s jednom ili više skupina neovisno odabranih od: F, Cl, Br, I, CN, OH, OCH3 i SO2CH3;
Rb je neovisno odabran od sljedećih: H, −O(C1-C3 alkil), C1-C6 alkil, C2-C8 alkenil, propargil, −(C1-C6 alkildiil)-(C3-C6 cikloalkil), C3-C6 cikloalkil i C3-C6 heterociklil, opcijski supstituiran s jednom ili više skupina neovisno odabranih od: F, Cl, Br, I, CN, −CH2F, −CHF2, −CF3, −CH2CF3, −CH2CHF2, −CH2CH2F, OH, OCH3 i SO2CH3;
Rc je odabran od sljedećih: H, C1-C6 alkil, alil, propargil, opcijski supstituiran s jednom ili više skupina neovisno odabranih od sljedećih: F, Cl, Br, I, CN, OH, OCH3 i SO2CH3;
R1, R2, R3 i R4 su neovisno odabrani od sljedećih: H, F, Cl, Br, I, −CN, −CH3, −CH2CH3, −CH(CH3)2, −CH2CH(CH3)2, −CH2OH, −CH2OCH3, −CH2CH2OH, −C(CH3)2OH, −CH(OH)CH(CH3)2, −C(CH3)2CH2OH, −CH2CH2SO2CH3, −CH2OP(O)(OH)2, −CH2F, −CHF2, −CH2NH2, −CH2NHSO2CH3, −CH2NHCH3, −CH2N(CH3)2, −CF3, −CH2CF3, −CH2CHF2, −CH(CH3)CN, −C(CH3)2CN, −CH2CN, −CO2H, −COCH3, −CO2CH3, −CO2C(CH3)3, −COCH(OH)CH3, −CONH2, −CONHCH3, −CONHCH2CH3, −CONHCH(CH3)2, −CON(CH3)2, −C(CH3)2CONH2, −NH2, −NHCH3, −N(CH3)2, −NHCOCH3, −N(CH3)COCH3, −NHS(O)2CH3, −N(CH3)C(CH3)2CONH2, −N(CH3)CH2CH2S(O)2CH3, −NO2, =O, −OH, −OCH3, −OCH2CH3, −OCH2CH2OCH3, −OCH2CH2OH, −OCH2CH2N(CH3)2, −OP(O)(OH)2, −S(O)2N(CH3)2, −SCH3, −S(O)2CH3, −S(O)3H, ciklopropil, ciklopropilamid, ciklobutil, oksetanil, azetidinil, 1-metilazetidin-3-il)oksi, N-metil-N-oksetan-3-ilamino, azetidin-1-ilmetil, benziloksifenil, pirolidin-1-il, pirolidin-1-il-metanon, piperazin-1-il, morfolinometil, morfolino-metanon i morfolino;
R5 je odabran od sljedećih: H, C1-C9 alkil, C3-C9 cikloalkil, C3-C9 heterocikl, C6-C9 aril, C6-C9 heteroaril, −(C1-C6 alkildiil)-(C3-C9 cikloalkil), −(C1-C6 alkildiil)-(C3-C9 heterocikl), C(O)Rb, C(O)NRa, SO2Ra i SO2NRa, opcijski supstituiran s jednim ili više halogena, CN, ORa, N(Ra)2, C1-C9 alkila, C3-C9 cikloalkila, C3-C9 heterocikla, C6-C9 arila, C6-C9 heteroarila, C(O)Rb, C(O)NRa, SO2Ra i SO2NRa;
R6 je odabran od sljedećih: F, Cl, Br, I, −CN, −CH3, −CH2CH3, −CH(CH3)2, −CH2CH(CH3)2, −CH2OH, −CH2OCH3, −CH2CH2OH, −C(CH3)2OH, −CH(OH)CH(CH3)2, −C(CH3)2CH2OH, −CH2CH2SO2CH3, −CH2OP(O)(OH)2, −CH2F, −CHF2, −CH2NH2, −CH2NHSO2CH3, −CH2NHCH3, −CH2N(CH3)2, −CF3, −CH2CF3, −CH2CHF2, −CH2CH2F, −CH(CH3)CN, −C(CH3)2CN, −CH2CN, −CO2H, −COCH3, −CO2CH3, −CO2C(CH3)3, −COCH(OH)CH3, −CONH2, −CONHCH3, −CONHCH2CH3, −CONHCH(CH3)2, −CON(CH3)2, −C(CH3)2CONH2, −NH2, −NHCH3, −N(CH3)2, −NHCOCH3, −N(CH3)COCH3, −NHS(O)2CH3, −N(CH3)C(CH3)2CONH2, −N(CH3)CH2CH2S(O)2CH3, −NO2, =O, −OH, −OCH3, −OCH2CH3, −OCH2CH2OCH3, −OCH2CH2OH, −OCH2CH2N(CH3)2, −OP(O)(OH)2, −S(O)2N(CH3)2, −SCH3, −S(O)2CH3, −S(O)3H, ciklopropil, ciklopropilamid, ciklobutil, oksetanil, azetidinil, 1-metilazetidin-3-il)oksi, N-metil-N-oksetan-3-ilamino, azetidin-1-ilmetil, benziloksifenil, pirolidin-1-il, pirolidin-1-il-metanon, piperazin-1-il, morfolinometil, morfolino-metanon i morfolino;
R7 je F, Cl, Br, I, −CN, −CH3, −CH2CH3, −CH(CH3)2, −CH2CH(CH3)2, −CH2OH, −CH2OCH3, −CH2CH2OH, −C(CH3)2OH, −CH(OH)CH(CH3)2, −C(CH3)2CH2OH, −CH2CH2SO2CH3, −CH2OP(O)(OH)2, −CH2F, −CHF2, −CH2NH2, −CH2NHSO2CH3, −CH2NHCH3, −CH2N(CH3)2, −CF3, −CH2CF3, −CH2CHF2, −CH(CH3)CN, −C(CH3)2CN, −CH2CN, −CO2H, −COCH3, −CO2CH3, −CO2C(CH3)3, −COCH(OH)CH3, −CONH2, −CONHCH3, −CONHCH2CH3, −CONHCH(CH3)2, −CON(CH3)2, −C(CH3)2CONH2, −NH2, −NHCH3, −N(CH3)2, −NHCOCH3, −N(CH3)COCH3, −NHS(O)2CH3, −N(CH3)C(CH3)2CONH2, −N(CH3)CH2CH2S(O)2CH3, −NO2, =O, −OH, −OCH3, −OCH2CH3, −OCH2CH2OCH3, −OCH2CH2OH, −OCH2CH2N(CH3)2, −OP(O)(OH)2, −S(O)2N(CH3)2, −SCH3, −S(O)2CH3, −S(O)3H, ciklopropil, ciklopropilamid, oksetanil, azetidinil, 1-metilazetidin-3-il)oksi, N-metil-N-oksetan-3-ilamino, azetidin-1-ilmetil, benziloksifenil, pirolidin-1-il, pirolidin-1-il-metanon, piperazin-1-il, morfolinometil, morfolino-metanon i morfolino;
m je odabran od 0, 1, 2, 3 i 4; i
n je odabran od 0, 1, 2, 3 i 4;
pri čemu su alkildiil, arildiil, karbociklildiil, heterociklildiil i heteroarildiil opcijski supstituirani s jednom ili više skupina neovisno odabranih od sljedećih: F, Cl, Br, I, −CN, −CH3, −CH2CH3, −CH(CH3)2, −CH2CH(CH3)2, −CH2OH, −CH2OCH3, −CH2CH2OH, −C(CH3)2OH, −CH(OH)CH(CH3)2, −C(CH3)2CH2OH, −CH2CH2SO2CH3, −CH2OP(O)(OH)2, −CH2F, −CHF2, −CF3, −CH2CF3, −CH2CHF2, −CH2CH2F, −CH(CH3)CN, −C(CH3)2CN, −CH2CN, −CH2NH2, −CH2NHSO2CH3, −CH2NHCH3, −CH2N(CH3)2, −CO2H, −COCH3, −CO2CH3, −CO2C(CH3)3, −COCH(OH)CH3, −CONH2, −CONHCH3, −CON(CH3)2, −C(CH3)2CONH2, −NH2, −NHCH3, −N(CH3)2, −NHCOCH3, −N(CH3)COCH3, −NHS(O)2CH3, −N(CH3)C(CH3)2CONH2, −N(CH3)CH2CH2S(O)2CH3, −NO2, =O, −OH, −OCH3, −OCH2CH3, −OCH2CH2OCH3, −OCH2CH2OH, −OCH2CH2N(CH3)2, −OP(O)(OH)2, −S(O)2N(CH3)2, −SCH3, −S(O)2CH3, −S(O)3H, ciklopropil, ciklopropilamid, ciklobutil, oksetanil, azetidinil, 1-metilazetidin-3-il)oksi, N-metil-N-oksetan-3-ilamino, azetidin-1-ilmetil, benziloksifenil, pirolidin-1-il, pirolidin-1-il-metanon, piperazin-1-il, morfolinometil, morfolino-metanon i morfolino.
2. Spoj prema patentnom zahtjevu 1, naznačen time, da Rc je H.
3. Spoj prema patentnom zahtjevu 1, naznačen time, da R1 i R2 su H.
4. Spoj prema patentnom zahtjevu 1, naznačen time, da R3 je H, a R4 je −CH3.
5. Spoj prema patentnom zahtjevu 1, naznačen time, da R5 je C1-C6 fluoroalkil.
6. Spoj prema patentnom zahtjevu 1, naznačen time, da m je 0.
7. Spoj prema patentnom zahtjevu 1, naznačen time, da je odabran od sljedećih:
N-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-metilpropil)-3-metil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
(R)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol;
(S)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol;
(R)-2-fluoro-3-((1R,3R)-1-(2-fluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-metilpropan-1-ol;
(S)-2-fluoro-3-((1R,3R)-1-(2-fluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-metilpropan-1-ol;
(R)-2-fluoro-3-((1R,3R)-1-(4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-metilpropan-1-ol;
(S)-2-fluoro-3-((1R,3R)-1-(4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-metilpropan-1-ol;
N-(3,5-difluoro-4-((1R,3R)-3-metil-2-(2,2,2-trifluoroetil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
1-(3-fluoropropil)-N-[4-[(1R,3R)-3-metil-2-metilsulfonil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]fenil]azetidin-3-amin;
N-[3,5-difluoro-4-[(1R,3R)-3-metil-2-metilsulfonil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]fenil]-1-(3-fluoropropil)azetidin-3-amin;
1-(3-fluoropropil)-N-[4-[(1S,3R)-3-metil-2-metilsulfonil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]fenil]azetidin-3-amin;
N-[3,5-difluoro-4-[(1S,3R)-3-metil-2-metilsulfonil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]fenil]-1-(3-fluoropropil)azetidin-3-amin;
3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2,2-difluoro-propan-1-ol;
(2R)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2-metil-propanska kiselina;
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-difluoropropan-1-ol;
3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-difluoropropan-1-ol;
(2S)-3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2-metil-propanska kiselina;
N-(3,5-difluoro-4-((1R,3R)-6-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1S,3S)-6-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-dimetilpropanska kiselina;
N-(3,5-difluoro-4-((1R,3R)-6-fluoro-3-metil-2-(metilsulfonil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1S,3S)-6-fluoro-3-metil-2-(metilsulfonil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(4-((1R,3R)-2-(2,2-difluoroetil)-6-fluoro-3-metil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)-3,5-difluorofenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(4-((1S,3S)-2-(2,2-difluoroetil)-6-fluoro-3-metil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)-3,5-difluorofenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1R,3R)-7-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1S,3S)-7-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
(S)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(R)-3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(R)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(S)-3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
N-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-metilpropil)-3-metil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)-N-metilazetidin-3-amin;
(R)-N-(4-(2-(2,2-difluoroetil)-3,3-dimetil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)-3,5-difluorofenil)-1-(3-fluoropropil)azetidin-3-amin;
(S)-N-(4-(2-(2,2-difluoroetil)-3,3-dimetil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)-3,5-difluorofenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1R,3R)-5-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1S,3S)-5-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1S,3S)-8-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
N-(3,5-difluoro-4-((1R,3R)-8-fluoro-3-metil-2-(2,2,2-trifluoretil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin;
(S)-3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(R)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(S)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
(R)-3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-metilpropan-1-ol;
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-5-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
(R)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-(hidroksimetil)propan-nitril;
(S)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2-fluoro-2-(hidroksimetil)propan-nitril;
(R)-3-(1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3,3-dimetil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
(S)-3-(1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-3,3-dimetil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-8-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-8-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-7-fluoro-3-metil-3,4-dihidro-1H-pirido[3,4-b]indol-2(9H)-il)-2,2-difluoropropan-1-ol;
N-[4-[(1R,3R)-2-(2,2-difluoroetil)-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]-
3,5-difluoro-fenil]-1-(3-fluoropropil)azetidin-3-amin;
(R)-3-((2R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol;
(S)-3-((1S,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol;
(S)-3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol;
(R)-3-((1R,3S)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2-fluoro-2-metilpropan-1-ol.
8. Spoj formule Ih prema patentnom zahtjevu 1, ili njegovih farmaceutski prihvatljivih soli, naznačen time, da spoj formule Ih je 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2,2-difluoro-propan-1-ol ili njegova farmaceutski prihvatljiva sol
[image]
9. Spoj formule Ih prema patentnom zahtjevu 1, naznačen time, da spoj formule Ih je 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2,2-difluoro-propan-1-ol
[image]
10. Farmaceutski prihvatljiva sol spoja formule Ih prema patentnom zahtjevu 1, naznačena time, da spoj formule Ih je 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropil)azetidin-3-il]amino]fenil]-3-metil-1,3,4,9-tetrahidropirido[3,4-b]indol-2-il]-2,2-difluoro-propan-1-ol
[image]
11. Spoj formule Ih prema patentnom zahtjevu 1, ili njegovih farmaceutski prihvatljivih soli, naznačen time, da spoj formule Ih je 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-difluoropropan-1-ol ili njegova farmaceutski prihvatljiva sol
[image]
12. Spoj formule Ih prema patentnom zahtjevu 1, naznačen time, da spoj formule Ih je 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-difluoropropan-1-ol
[image]
13. Farmaceutski prihvatljiva sol spoja formule Ih prema patentnom zahtjevu 1, naznačena time, da spoj formule Ih je 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropil)azetidin-3-il)amino)fenil)-6-fluoro-3-metil-1,3,4,9-tetrahidro-2H-pirido[3,4-b]indol-2-il)-2,2-difluoropropan-1-ol
[image]
14. Spoj formule Ih prema patentnom zahtjevu 1, ili njegovih farmaceutski prihvatljivih soli, naznačen time, da spoj formule Ih je N-(3,5-difluoro-4-((1R,3R)-7-fluoro-3-metil-2-(2,2,2-trifluoroetil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin ili njegova farmaceutski prihvatljiva sol
[image]
15. Spoj formule Ih prema patentnom zahtjevu 1, ili njegovih farmaceutski prihvatljivih soli, naznačen time, da spoj formule Ih je N-(3,5-difluoro-4-((1R,3R)-3-metil-2-(2,2,2-trifluoroetil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-il)fenil)-1-(3-fluoropropil)azetidin-3-amin ili njegova farmaceutski prihvatljiva sol
[image]
16. Farmaceutski pripravak, naznačen time, da sadrži spoj prema jednom od patentnih zahtjeva 1 do 15 i farmaceutski prihvatljivu pomoćnu tvar.
17. Spoj prema bilo kojem od patentnih zahtjeva 1 do 15, naznačen time, da se primjenjuje kao terapeutski aktivna tvar.
18. Spoj prema bilo kojem od patentnih zahtjeva 1 do 15, naznačen time, da se primjenjuje u liječenju bolesti ili poremećaja povezanog s ER-om, pri čemu navedena bolest ili poremećaj povezan s ER-om, je rak koji je odabran između raka dojke, raka pluća, raka jajnika, raka endometrija, raka prostate i raka maternice.
19. Spoj za primjenu prema patentnom zahtjevu 18, naznačen time, da rak je rak dojke.
20. Spoj za primjenu prema patentnom zahtjevu 19, naznačen time, da rak dojke je metastatski rak dojke koji je pozitivan na hormonski receptor.
21. Spoj za primjenu prema patentnom zahtjevu 19, naznačen time, da rak dojke je hormonalno ovisan rak dojke.
22. Spoj za primjenu prema patentnom zahtjevu 19, naznačen time, da rak dojke je rak dojke ovisan o estrogenskom receptoru.
23. Spoj za primjenu prema patentnom zahtjevu 19, naznačen time, da rak dojke je hormonski uporan rak dojke.
24. Spoj za primjenu prema bilo kojem od patentnih zahtjeva 19 do 23, naznačen time, da je rak rezistentan na antihormonsku terapiju.
25. Spoj za primjenu prema patentnom zahtjevu 24, naznačen time, da antihormonska terapija uključuje tamoksifen, fulvestrant, steroidne inhibitore aromataze ili nesteroidne inhibitore aromataze.
26. Spoj za primjenu prema patentnom zahtjevu 19, naznačen time, da rak dojke nikada nije liječen kemoterapijom.
27. Spoj za primjenu prema bilo kojem od patentnih zahtjeva 19 do 26, naznačen time, da se spoj daje u kombinaciji s inhibitorom CDK4/6.
28. Spoj za primjenu prema patentnom zahtjevu 27, naznačen time, da je inhibitor CDK4/6 palbociklib, ribociklib ili LY283519.
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PCT/EP2015/080119 WO2016097072A1 (en) | 2014-12-18 | 2015-12-17 | TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF |
EP15810660.9A EP3233852B1 (en) | 2014-12-18 | 2015-12-17 | Tetrahydro-pyrido[3,4-b]indoles as estrogen receptor modulators and uses thereof |
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