JP2019510799A5 - - Google Patents
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- JP2019510799A5 JP2019510799A5 JP2018552850A JP2018552850A JP2019510799A5 JP 2019510799 A5 JP2019510799 A5 JP 2019510799A5 JP 2018552850 A JP2018552850 A JP 2018552850A JP 2018552850 A JP2018552850 A JP 2018552850A JP 2019510799 A5 JP2019510799 A5 JP 2019510799A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- phenyl
- azetidine
- ethoxy
- fluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 97
- -1 1-Methylazetidine-3-yl Chemical group 0.000 claims description 52
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 8
- 125000003566 oxetanyl group Chemical group 0.000 claims description 8
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 6
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims description 4
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 18
- 229940124597 therapeutic agent Drugs 0.000 claims 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 6
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 4
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 4
- BXLHOSHUHPPGDV-UHFFFAOYSA-N 1h-azepin-2-ol Chemical compound OC1=CC=CC=CN1 BXLHOSHUHPPGDV-UHFFFAOYSA-N 0.000 claims 3
- DFVXEZWOASLALX-JOCHJYFZSA-N (1R)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FC1=C(C(=CC(=C1)OCCN1CC(C1)CF)F)[C@@H]1N(CCC2=CC(=CC=C12)O)CC(F)(F)F DFVXEZWOASLALX-JOCHJYFZSA-N 0.000 claims 2
- VLOSTMAVKBAZEM-HSZRJFAPSA-N (1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-1-methyl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@]1(N(CCC2=CC(=CC=C12)O)CC(F)(F)F)C VLOSTMAVKBAZEM-HSZRJFAPSA-N 0.000 claims 2
- DWFGIGKAFDWCKR-JOCHJYFZSA-N (1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinoline-6-carboxamide Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N(CCC2=CC(=CC=C12)C(=O)N)CC(F)(F)F DWFGIGKAFDWCKR-JOCHJYFZSA-N 0.000 claims 2
- JWUOZESJFTULNI-AREMUKBSSA-N (1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-1-methyl-3,4-dihydroisoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@]1(N(CCC2=CC(=CC=C12)O)CC(C)(C)F)C JWUOZESJFTULNI-AREMUKBSSA-N 0.000 claims 2
- ALHSDDHUURUUFF-XMMPIXPASA-N (1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FC(CN1[C@@H](C2=CC=C(C=C2CC1)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)(C)C ALHSDDHUURUUFF-XMMPIXPASA-N 0.000 claims 2
- GYPXHXYCRMGLOU-HSZRJFAPSA-N (1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3,3-dimethyl-2-(2,2,2-trifluoroethyl)-1,4-dihydroisoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N(C(CC2=CC(=CC=C12)O)(C)C)CC(F)(F)F GYPXHXYCRMGLOU-HSZRJFAPSA-N 0.000 claims 2
- CLVNGZILSMJZDX-XMMPIXPASA-N (1R)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-1-methyl-3,4-dihydroisoquinolin-6-ol Chemical compound FC(CN1[C@](C2=CC=C(C=C2CC1)O)(C)C1=CC=C(C=C1)OCCN1CC(C1)CF)(CO)F CLVNGZILSMJZDX-XMMPIXPASA-N 0.000 claims 2
- BNQXMOBIGDCFOW-NFQMXDRXSA-N (1R)-2-(2-fluoro-2-methylpropyl)-1-methyl-1-[4-[2-[(3R)-3-methylpyrrolidin-1-yl]ethoxy]phenyl]-3,4-dihydroisoquinolin-6-ol Chemical compound FC(CN1[C@@](C2=CC=C(C=C2CC1)O)(C1=CC=C(C=C1)OCCN1C[C@@H](CC1)C)C)(C)C BNQXMOBIGDCFOW-NFQMXDRXSA-N 0.000 claims 2
- BKBDCKCPOHJNMA-WAIKUNEKSA-N (1R,3R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N([C@@H](CC2=CC(=CC=C12)O)C)CC(F)(F)F BKBDCKCPOHJNMA-WAIKUNEKSA-N 0.000 claims 2
- KTLXJZWWYPXZBP-UZUQRXQVSA-N (1R,3R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinoline Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N([C@@H](CC2=CC=CC=C12)C)CC(F)(F)F KTLXJZWWYPXZBP-UZUQRXQVSA-N 0.000 claims 2
- JMKZMWGLYQTHCM-MZNJEOGPSA-N (1R,3R)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FC(CN1[C@@H](C2=CC=C(C=C2C[C@H]1C)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)(CO)F JMKZMWGLYQTHCM-MZNJEOGPSA-N 0.000 claims 2
- PTNXVMQCPOSHGP-MZNJEOGPSA-N (1R,3R)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinolin-8-ol Chemical compound C[C@@H]1CC2=C([C@H](N1CC(F)(F)CO)C1=CC=C(OCCN3CC(CF)C3)C=C1)C(O)=CC=C2 PTNXVMQCPOSHGP-MZNJEOGPSA-N 0.000 claims 2
- KUSGGKASIHPZQJ-MZNJEOGPSA-N (1R,3R)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinoline-6-sulfonamide Chemical compound C[C@@H]1CC2=C(C=CC(=C2)S(N)(=O)=O)[C@H](N1CC(F)(F)CO)C1=CC=C(OCCN2CC(CF)C2)C=C1 KUSGGKASIHPZQJ-MZNJEOGPSA-N 0.000 claims 2
- DABPJEVISFOUNE-QMHKHESXSA-N (1R,4R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-4-methyl-2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N(C[C@@H](C2=CC(=CC=C12)O)C)S(=O)(=O)C DABPJEVISFOUNE-QMHKHESXSA-N 0.000 claims 2
- DABPJEVISFOUNE-WAIKUNEKSA-N (1R,4S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-4-methyl-2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N(C[C@H](C2=CC(=CC=C12)O)C)S(=O)(=O)C DABPJEVISFOUNE-WAIKUNEKSA-N 0.000 claims 2
- DFVXEZWOASLALX-QFIPXVFZSA-N (1S)-1-[2,6-difluoro-4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FC1=C(C(=CC(=C1)OCCN1CC(C1)CF)F)[C@H]1N(CCC2=CC(=CC=C12)O)CC(F)(F)F DFVXEZWOASLALX-QFIPXVFZSA-N 0.000 claims 2
- DWFGIGKAFDWCKR-QFIPXVFZSA-N (1S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinoline-6-carboxamide Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N(CCC2=CC(=CC=C12)C(=O)N)CC(F)(F)F DWFGIGKAFDWCKR-QFIPXVFZSA-N 0.000 claims 2
- JWUOZESJFTULNI-SANMLTNESA-N (1S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2-fluoro-2-methylpropyl)-1-methyl-3,4-dihydroisoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@]1(N(CCC2=CC(=CC=C12)O)CC(C)(C)F)C JWUOZESJFTULNI-SANMLTNESA-N 0.000 claims 2
- CLVNGZILSMJZDX-DEOSSOPVSA-N (1S)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-1-methyl-3,4-dihydroisoquinolin-6-ol Chemical compound FC(CN1[C@@](C2=CC=C(C=C2CC1)O)(C)C1=CC=C(C=C1)OCCN1CC(C1)CF)(CO)F CLVNGZILSMJZDX-DEOSSOPVSA-N 0.000 claims 2
- BNQXMOBIGDCFOW-HRFSGMKKSA-N (1S)-2-(2-fluoro-2-methylpropyl)-1-methyl-1-[4-[2-[(3R)-3-methylpyrrolidin-1-yl]ethoxy]phenyl]-3,4-dihydroisoquinolin-6-ol Chemical compound FC(CN1[C@](C2=CC=C(C=C2CC1)O)(C1=CC=C(C=C1)OCCN1C[C@@H](CC1)C)C)(C)C BNQXMOBIGDCFOW-HRFSGMKKSA-N 0.000 claims 2
- UEMRZFLCPNBOQA-MWTRTKDXSA-N (1S,3R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N([C@@H](CC2=CC(=CC=C12)O)C)S(=O)(=O)C UEMRZFLCPNBOQA-MWTRTKDXSA-N 0.000 claims 2
- KTLXJZWWYPXZBP-SBUREZEXSA-N (1S,3S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinoline Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N([C@H](CC2=CC=CC=C12)C)CC(F)(F)F KTLXJZWWYPXZBP-SBUREZEXSA-N 0.000 claims 2
- VOYGBWDJGBJHDH-HJPURHCSSA-N (1S,3S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinoline-6-carboxylic acid Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N([C@H](CC2=CC(=CC=C12)C(=O)O)C)CC(F)(F)F VOYGBWDJGBJHDH-HJPURHCSSA-N 0.000 claims 2
- UEMRZFLCPNBOQA-HJPURHCSSA-N (1S,3S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N([C@H](CC2=CC(=CC=C12)O)C)S(=O)(=O)C UEMRZFLCPNBOQA-HJPURHCSSA-N 0.000 claims 2
- JMKZMWGLYQTHCM-XDHUDOTRSA-N (1S,3S)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound C[C@H]1CC2=C(C=CC(O)=C2)[C@@H](N1CC(F)(F)CO)C1=CC=C(OCCN2CC(CF)C2)C=C1 JMKZMWGLYQTHCM-XDHUDOTRSA-N 0.000 claims 2
- PTNXVMQCPOSHGP-XDHUDOTRSA-N (1S,3S)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinolin-8-ol Chemical compound FC(CN1[C@H](C2=C(C=CC=C2C[C@@H]1C)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)(CO)F PTNXVMQCPOSHGP-XDHUDOTRSA-N 0.000 claims 2
- KUSGGKASIHPZQJ-XDHUDOTRSA-N (1S,3S)-2-(2,2-difluoro-3-hydroxypropyl)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-3-methyl-3,4-dihydro-1H-isoquinoline-6-sulfonamide Chemical compound FC(CN1[C@H](C2=CC=C(C=C2C[C@@H]1C)S(=O)(=O)N)C1=CC=C(C=C1)OCCN1CC(C1)CF)(CO)F KUSGGKASIHPZQJ-XDHUDOTRSA-N 0.000 claims 2
- DABPJEVISFOUNE-MWTRTKDXSA-N (1S,4S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-4-methyl-2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N(C[C@H](C2=CC(=CC=C12)O)C)S(=O)(=O)C DABPJEVISFOUNE-MWTRTKDXSA-N 0.000 claims 2
- AFHJGLYEFXWNLI-UHFFFAOYSA-N 1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-1-methyl-2-methylsulfonyl-3,4-dihydroisoquinolin-6-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)C1(N(CCC2=CC(=CC=C12)O)S(=O)(=O)C)C AFHJGLYEFXWNLI-UHFFFAOYSA-N 0.000 claims 2
- DOKAKZWDBYSGJO-UYXZNNOOSA-N 2,2-difluoro-3-[(1R,3R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-6-[(1S)-1-hydroxyethyl]-3-methyl-3,4-dihydro-1H-isoquinolin-2-yl]propan-1-ol Chemical compound FC(CO)(CN1[C@@H](C2=CC=C(C=C2C[C@H]1C)[C@H](C)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)F DOKAKZWDBYSGJO-UYXZNNOOSA-N 0.000 claims 2
- ZKQHQMPYZQYLCG-BVZFJXPGSA-N 2,2-difluoro-3-[(1S,3S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-6-(hydroxymethyl)-3-methyl-3,4-dihydro-1H-isoquinolin-2-yl]propan-1-ol Chemical compound FC(CO)(CN1[C@H](C2=CC=C(C=C2C[C@@H]1C)CO)C1=CC=C(C=C1)OCCN1CC(C1)CF)F ZKQHQMPYZQYLCG-BVZFJXPGSA-N 0.000 claims 2
- DOKAKZWDBYSGJO-DGUDUIIESA-N 2,2-difluoro-3-[(1S,3S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-6-[(1S)-1-hydroxyethyl]-3-methyl-3,4-dihydro-1H-isoquinolin-2-yl]propan-1-ol Chemical compound FC(CO)(CN1[C@H](C2=CC=C(C=C2C[C@@H]1C)[C@H](C)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)F DOKAKZWDBYSGJO-DGUDUIIESA-N 0.000 claims 2
- HAWGBQHBOGNATE-HSZRJFAPSA-N 2-fluoro-1-[(1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-6-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl]-2-methylpropan-1-one Chemical compound FC(C(=O)N1[C@@H](C2=CC=C(C=C2CC1)O)C1=CC=C(C=C1)OCCN1CC(C1)CF)(C)C HAWGBQHBOGNATE-HSZRJFAPSA-N 0.000 claims 2
- HAWGBQHBOGNATE-QHCPKHFHSA-N 2-fluoro-1-[(1S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-6-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl]-2-methylpropan-1-one Chemical compound CC(C)(F)C(=O)N1CCC2=C(C=CC(O)=C2)[C@@H]1C1=CC=C(OCCN2CC(CF)C2)C=C1 HAWGBQHBOGNATE-QHCPKHFHSA-N 0.000 claims 2
- XUNUAWWTPDXMAL-AREMUKBSSA-N 4-[(1R)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinolin-6-yl]morpholine Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@H]1N(CCC2=CC(=CC=C12)N1CCOCC1)CC(F)(F)F XUNUAWWTPDXMAL-AREMUKBSSA-N 0.000 claims 2
- XUNUAWWTPDXMAL-SANMLTNESA-N 4-[(1S)-1-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-isoquinolin-6-yl]morpholine Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N(CCC2=CC(=CC=C12)N1CCOCC1)CC(F)(F)F XUNUAWWTPDXMAL-SANMLTNESA-N 0.000 claims 2
- 208000019838 Blood disease Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- LPSWHJANNYROHR-SANMLTNESA-N FC([C@]1(N(CCC2=CC(=CC=C12)O)CC(C)(C)F)C1=CC=C(C=C1)OCCN1CC(C1)CF)F Chemical compound FC([C@]1(N(CCC2=CC(=CC=C12)O)CC(C)(C)F)C1=CC=C(C=C1)OCCN1CC(C1)CF)F LPSWHJANNYROHR-SANMLTNESA-N 0.000 claims 2
- IWCNMGHVEYTYJN-YHAMSUFESA-N FC1=C(C(=CC(=C1)OCCN1CC(C1)CF)F)[C@@H]1N([C@H](CC2=C3C(=CC=C12)NN=C3)C)CC(C)(C)F Chemical compound FC1=C(C(=CC(=C1)OCCN1CC(C1)CF)F)[C@@H]1N([C@H](CC2=C3C(=CC=C12)NN=C3)C)CC(C)(C)F IWCNMGHVEYTYJN-YHAMSUFESA-N 0.000 claims 2
- GYPXHXYCRMGLOU-QHCPKHFHSA-N FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N(C(CC2=CC(=CC=C12)O)(C)C)CC(F)(F)F Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)[C@@H]1N(C(CC2=CC(=CC=C12)O)(C)C)CC(F)(F)F GYPXHXYCRMGLOU-QHCPKHFHSA-N 0.000 claims 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
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| UA125043C2 (uk) | 2017-01-30 | 2021-12-29 | Астразенека Аб | Модулятори рецептора естрогену |
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| EP3696178B1 (en) * | 2017-11-14 | 2022-04-06 | Kind Pharmaceutical | Heterocyclic compound and application thereof in medicine |
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| WO2020014440A1 (en) * | 2018-07-12 | 2020-01-16 | Eli Lilly And Company | Selective estrogen receptor degraders |
| CN111499614A (zh) * | 2019-01-31 | 2020-08-07 | 江苏恒瑞医药股份有限公司 | 四氢异喹啉类衍生物、其制备方法及其在医药上的应用 |
| US12428428B2 (en) | 2020-01-10 | 2025-09-30 | Jiangsu Hengrui Medicine Co., Ltd. | Tricyclic tetrahydroisoquinoline derivative, preparation method therefor and application thereof in medicine |
| WO2021213358A1 (zh) * | 2020-04-21 | 2021-10-28 | 江苏先声药业有限公司 | 含硼化合物及其应用 |
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| CN111825613B (zh) * | 2020-08-17 | 2022-02-15 | 上海勋和医药科技有限公司 | 作为选择性雌激素受体下调剂的四氢异喹啉类化合物、合成方法及用途 |
| CN114105977B (zh) * | 2020-08-28 | 2023-09-01 | 先声再明医药有限公司 | 雌激素受体调节剂化合物及其用途 |
| WO2022166980A1 (zh) * | 2021-02-08 | 2022-08-11 | 贝达药业股份有限公司 | 杂芳基并哌啶类衍生物及其药物组合物和应用 |
| US20240150294A1 (en) * | 2021-02-19 | 2024-05-09 | The University Of Chicago | Estrogen receptor alpha antagonists and uses thereof |
| CN113024460B (zh) * | 2021-03-10 | 2022-11-08 | 中国药科大学 | 作为雌激素受体与组蛋白去乙酰化酶双靶点化合物的四氢异喹啉类化合物、合成方法及用途 |
| JP7605536B2 (ja) * | 2021-03-15 | 2024-12-24 | 深▲せん▼福沃薬業有限公司 | エストロゲン受容体モジュレーター |
| TW202317582A (zh) * | 2021-07-09 | 2023-05-01 | 大陸商江蘇恒瑞醫藥股份有限公司 | 三環四氫異喹啉類衍生物的鹽型 |
| WO2023284837A1 (zh) * | 2021-07-15 | 2023-01-19 | 四川海思科制药有限公司 | 芳氨基衍生物雌激素受体调节剂及其用途 |
| CN119790048A (zh) * | 2022-08-25 | 2025-04-08 | 赛诺菲 | 新颖的取代的四氢异喹啉-6-甲酸衍生物、用于其制备的方法及其治疗用途 |
| CN115252606B (zh) * | 2022-09-29 | 2023-02-03 | 北京市神经外科研究所 | 化合物在制备用于治疗肿瘤的药物中的应用 |
| WO2025209455A1 (zh) * | 2024-04-01 | 2025-10-09 | 山东盛迪医药有限公司 | 一种选择性雌激素受体降解剂的制备方法 |
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| US5981521A (en) * | 1998-11-13 | 1999-11-09 | Abbott Laboratories | Tetrahydroisoquinoline derivatives as LHRH antagonists |
| WO2000055137A1 (en) * | 1999-03-17 | 2000-09-21 | Signal Pharmaceuticals, Inc. | Compounds and methods for modulation of estrogen receptors |
| GB0000313D0 (en) | 2000-01-10 | 2000-03-01 | Astrazeneca Uk Ltd | Formulation |
| CA2408486A1 (en) * | 2000-05-11 | 2001-11-15 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline analogs useful as growth hormone secretagogues |
| JP2004515494A (ja) * | 2000-12-07 | 2004-05-27 | アストラゼネカ・アクチエボラーグ | 治療剤 |
| ES2586908T3 (es) * | 2010-12-24 | 2016-10-19 | Merck Sharp & Dohme B.V. | Derivados de azetidina N-sustituidos |
| CN102875466A (zh) * | 2012-04-23 | 2013-01-16 | 中国药科大学 | 异喹啉酮衍生物,其制备方法及其医药用途 |
| WO2015092634A1 (en) * | 2013-12-16 | 2015-06-25 | Novartis Ag | 1,2,3,4-tetrahydroisoquinoline compounds and compositions as selective estrogen receptor antagonists and degraders |
| JP6807841B2 (ja) * | 2014-12-18 | 2021-01-06 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | エストロゲン受容体モジュレーター及びその使用 |
| WO2017182493A1 (en) * | 2016-04-20 | 2017-10-26 | Astrazeneca Ab | Indazole derivatives for use in down-regulation of the estrogen receptor for the treatment of cancer |
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