JP2021502987A5 - - Google Patents
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- Publication number
- JP2021502987A5 JP2021502987A5 JP2020526530A JP2020526530A JP2021502987A5 JP 2021502987 A5 JP2021502987 A5 JP 2021502987A5 JP 2020526530 A JP2020526530 A JP 2020526530A JP 2020526530 A JP2020526530 A JP 2020526530A JP 2021502987 A5 JP2021502987 A5 JP 2021502987A5
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- ylmethoxy
- isoquinoline
- dioxane
- pyrimid
- 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.)
- Pending
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- -1 [1,4] dioxane-2-ylmethoxy Chemical group 0.000 description 568
- DZOKENUNRMDZCS-UHFFFAOYSA-N 3h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)CN=CC2=C1 DZOKENUNRMDZCS-UHFFFAOYSA-N 0.000 description 373
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 130
- 125000000217 alkyl group Chemical group 0.000 description 33
- 229910052760 oxygen Inorganic materials 0.000 description 32
- 229910052717 sulfur Inorganic materials 0.000 description 29
- 125000005842 heteroatom Chemical group 0.000 description 27
- 125000005843 halogen group Chemical group 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 23
- 150000003839 salts Chemical class 0.000 description 19
- 125000003545 alkoxy group Chemical group 0.000 description 17
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 14
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 8
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 description 4
- 230000003176 fibrotic effect Effects 0.000 description 4
- 125000001475 halogen functional group Chemical group 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- 125000004450 alkenylene group Chemical group 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 description 2
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- BAJAQTZUNKFUHC-QHCPKHFHSA-N 1-cyclopropyl-2-[[(2S)-1,4-dioxan-2-yl]methoxy]-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O=C1C=C(OC[C@@H]2COCCO2)C(C2CC2)=C2N1CCC1=C2C=CC(OCC2=CC=CC=C2)=C1 BAJAQTZUNKFUHC-QHCPKHFHSA-N 0.000 description 1
- KPFHQSQJQMNXRD-UHFFFAOYSA-N 10-(2,2-difluoroethoxy)-9-methoxy-1-methyl-2-(oxan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound FC(COC1=C(C=C2CCN3C(C2=C1)=C(C(=CC3=O)OCC1OCCCC1)C)OC)F KPFHQSQJQMNXRD-UHFFFAOYSA-N 0.000 description 1
- BPEJEBDBKQQGPV-AWEZNQCLSA-N 10-(difluoromethylsulfanyl)-2-[[(2S)-1,4-dioxan-2-yl]methoxy]-9-methoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C=C1SC(F)F)C1=C(C)C(OC[C@@H]3COCCO3)=CC(=O)N1CC2 BPEJEBDBKQQGPV-AWEZNQCLSA-N 0.000 description 1
- QLGXULPFEWAIAS-UHFFFAOYSA-N 10-hydroxy-9-methoxy-1-methyl-2-(oxan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound OC1=C(C=C2CCN3C(C2=C1)=C(C(=CC3=O)OCC1OCCCC1)C)OC QLGXULPFEWAIAS-UHFFFAOYSA-N 0.000 description 1
- LTYWSRLCEJRSDU-UHFFFAOYSA-N 10-hydroxy-9-methoxy-1-methyl-2-(oxan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COc1cc2CCn3c(c(C)c(NCC4CCCCO4)cc3=O)-c2cc1O LTYWSRLCEJRSDU-UHFFFAOYSA-N 0.000 description 1
- 125000004909 2,2-dimethylbutylamino group Chemical group CC(CN*)(CC)C 0.000 description 1
- NEGUMAHLBUAVIX-PMACEKPBSA-N 2,9-bis[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC1=C2N(CCC3=C2C=CC(OC[C@@H]2COCCO2)=C3)C(=O)C=C1OC[C@@H]1COCCO1 NEGUMAHLBUAVIX-PMACEKPBSA-N 0.000 description 1
- CEIRHUANPUJLJS-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethoxy)-1,7,7-trimethyl-9-phenylmethoxy-6H-benzo[a]quinolizin-4-one Chemical compound CC1=C2N(CC(C)(C)C3=C2C=CC(OCC2=CC=CC=C2)=C3)C(=O)C=C1OCC1COCCO1 CEIRHUANPUJLJS-UHFFFAOYSA-N 0.000 description 1
- YEXUNIAGNHXOHY-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethoxy)-9,10-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C=C1OC)C1=CC(OCC3COCCO3)=CC(=O)N1CC2 YEXUNIAGNHXOHY-UHFFFAOYSA-N 0.000 description 1
- BIFGWDQBQGYDLR-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethylamino)-8,11-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC=C(OC)C2=C1CCN1C(=O)C=C(NCC3COCCO3)C=C21 BIFGWDQBQGYDLR-UHFFFAOYSA-N 0.000 description 1
- DFBFOMXPNGJADF-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethylamino)-8,9-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=C(OC)C2=C(C=C1)C1=C(C)C(NCC3COCCO3)=CC(=O)N1CC2 DFBFOMXPNGJADF-UHFFFAOYSA-N 0.000 description 1
- DVALFINDDISVAF-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethylamino)-8,9-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=C(OC)C2=C(C=C1)C1=CC(NCC3COCCO3)=CC(=O)N1CC2 DVALFINDDISVAF-UHFFFAOYSA-N 0.000 description 1
- XMAPDEWUHIOMLD-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethylamino)-9,10-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C=C1OC)C1=C(C)C(NCC3COCCO3)=CC(=O)N1CC2 XMAPDEWUHIOMLD-UHFFFAOYSA-N 0.000 description 1
- RWLIYEIGRXACFS-UHFFFAOYSA-N 2-(1,4-dioxan-2-ylmethylamino)-9,11-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C(OC)=C1)C1=CC(NCC3COCCO3)=CC(=O)N1CC2 RWLIYEIGRXACFS-UHFFFAOYSA-N 0.000 description 1
- YVKAVFAGZXYYGH-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-9,10-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C=C1OC)C1=C(C)C(OCC3COC4=CC=CC=C4O3)=CC(=O)N1CC2 YVKAVFAGZXYYGH-UHFFFAOYSA-N 0.000 description 1
- HRSSOJYPJQUCFX-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-9,10-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(C=C1OC)C1=CC(OCC3COC4=CC=CC=C4O3)=CC(=O)N1CC2 HRSSOJYPJQUCFX-UHFFFAOYSA-N 0.000 description 1
- NAWJHQMUQJIDLT-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-9-hydroxy-10-methoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(CCN3C(=O)C=C(OCC4COC5=CC=CC=C5O4)C=C23)C=C1O NAWJHQMUQJIDLT-UHFFFAOYSA-N 0.000 description 1
- MLWKQZZQYXSQQA-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-9-methoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COc1ccc-2c(CCn3c-2cc(OCC2COc4ccccc4O2)cc3=O)c1 MLWKQZZQYXSQQA-UHFFFAOYSA-N 0.000 description 1
- VZUVFZLHQSSKDJ-UHFFFAOYSA-N 2-(2,3-dihydrothieno[3,4-b][1,4]dioxin-3-ylmethoxy)-9,10-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O1C=2C(OCC1COC=1C=C3N(CCC4=CC(=C(C=C34)OC)OC)C(C=1)=O)=CSC=2 VZUVFZLHQSSKDJ-UHFFFAOYSA-N 0.000 description 1
- GTIPYGCAVQQPCI-UHFFFAOYSA-N 2-(cyclohexylmethoxy)-9,10-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound C1(CCCCC1)COC=1C(=C2N(CCC3=CC(=C(C=C23)OC)OC)C(C=1)=O)C GTIPYGCAVQQPCI-UHFFFAOYSA-N 0.000 description 1
- RRHAMYABAHYECW-FQEVSTJZSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1,7,7-trimethyl-9-pentyl-6H-benzo[a]quinolizin-4-one Chemical compound CCCCCC1=CC2=C(C=C1)C1=C(C)C(OC[C@@H]3COCCO3)=CC(=O)N1CC2(C)C RRHAMYABAHYECW-FQEVSTJZSA-N 0.000 description 1
- USKMINVCUYEPEJ-IBGZPJMESA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-ethyl-9-(1-methylpyrazol-4-yl)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CCC1=C2N(CCC3=C2C=CC(=C3)C2=CN(C)N=C2)C(=O)C=C1OC[C@@H]1COCCO1 USKMINVCUYEPEJ-IBGZPJMESA-N 0.000 description 1
- HTHBTGBYTFPMJO-INIZCTEOSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-ethyl-9-(2H-tetrazol-5-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CCC1=C2N(CCC3=C2C=CC(OCC2=NN=NN2)=C3)C(=O)C=C1OC[C@@H]1COCCO1 HTHBTGBYTFPMJO-INIZCTEOSA-N 0.000 description 1
- JSSBEOGNJUDSBA-OZBJMMHXSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-ethyl-9-(3-methoxybut-1-ynyl)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O1[C@@H](COCC1)COC=1C(=C2N(CCC3=CC(=CC=C23)C#CC(C)OC)C(C=1)=O)CC JSSBEOGNJUDSBA-OZBJMMHXSA-N 0.000 description 1
- GOPGZHYKKKOHDY-NRFANRHFSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-ethyl-9-(pyridin-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CCC1=C2N(CCC3=C2C=CC(OCC2=NC=CC=C2)=C3)C(=O)C=C1OC[C@@H]1COCCO1 GOPGZHYKKKOHDY-NRFANRHFSA-N 0.000 description 1
- YJTIKENBYXAQBD-HNNXBMFYSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-ethyl-9-hydroxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CCC1=C2N(CCC3=C2C=CC(O)=C3)C(=O)C=C1OC[C@@H]1COCCO1 YJTIKENBYXAQBD-HNNXBMFYSA-N 0.000 description 1
- BSJVLZYYAKJGBK-INIZCTEOSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-4-oxo-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizine-10-carbonitrile Chemical compound CC1=C2N(CCC3=C2C=C(C#N)C(OCC(F)(F)F)=C3)C(=O)C=C1OC[C@@H]1COCCO1 BSJVLZYYAKJGBK-INIZCTEOSA-N 0.000 description 1
- PAAHDXBWZAWRBD-IBGZPJMESA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-(1-methylpyrazol-4-yl)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CN1C=C(C=N1)C1=CC2=C(C=C1)C1=C(C)C(OC[C@@H]3COCCO3)=CC(=O)N1CC2 PAAHDXBWZAWRBD-IBGZPJMESA-N 0.000 description 1
- HXPVTGJORJIVGA-FQEVSTJZSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-(3-methylbutyl)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC(C)CCC1=CC2=C(C=C1)C1=C(C)C(OC[C@@H]3COCCO3)=CC(=O)N1CC2 HXPVTGJORJIVGA-FQEVSTJZSA-N 0.000 description 1
- WVEJVSIVGCGHJW-FQEVSTJZSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-(oxan-4-yl)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC1=C2N(CCC3=C2C=CC(=C3)C2CCOCC2)C(=O)C=C1OC[C@@H]1COCCO1 WVEJVSIVGCGHJW-FQEVSTJZSA-N 0.000 description 1
- GCCULZDRGLDULQ-NRFANRHFSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-(pyridin-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC1=C2N(CCC3=C2C=CC(OCC2=NC=CC=C2)=C3)C(=O)C=C1OC[C@@H]1COCCO1 GCCULZDRGLDULQ-NRFANRHFSA-N 0.000 description 1
- MBKBTQNYMPIMGC-IBGZPJMESA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-[(1-propyltetrazol-5-yl)methoxy]-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CCCN1N=NN=C1COC1=CC2=C(C=C1)C1=C(C)C(OC[C@@H]3COCCO3)=CC(=O)N1CC2 MBKBTQNYMPIMGC-IBGZPJMESA-N 0.000 description 1
- UJPBLACCBXCYNM-IBGZPJMESA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-9-[(3-methyloxetan-3-yl)methoxy]-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC1=C2N(CCC3=C2C=CC(OCC2(C)COC2)=C3)C(=O)C=C1OC[C@@H]1COCCO1 UJPBLACCBXCYNM-IBGZPJMESA-N 0.000 description 1
- JDJSAARCKFSUKO-INIZCTEOSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-10-methoxy-1-methyl-4-oxo-6,7-dihydrobenzo[a]quinolizine-9-carbonitrile Chemical compound O1[C@@H](COCC1)COC=1C(=C2N(CCC3=CC(=C(C=C23)OC)C#N)C(C=1)=O)C JDJSAARCKFSUKO-INIZCTEOSA-N 0.000 description 1
- WNECPCJEQRXXRJ-INIZCTEOSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-10-methoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COc1ccc2CCn3c(c(C)c(OC[C@@H]4COCCO4)cc3=O)-c2c1 WNECPCJEQRXXRJ-INIZCTEOSA-N 0.000 description 1
- BNIQDFUYKUMOSU-FQEVSTJZSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-10-methoxy-1-methyl-9-[4-(trifluoromethoxy)phenyl]-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound COC1=CC2=C(CCN3C(=O)C=C(OC[C@@H]4COCCO4)C(C)=C23)C=C1C1=CC=C(OC(F)(F)F)C=C1 BNIQDFUYKUMOSU-FQEVSTJZSA-N 0.000 description 1
- AYHBSEIGOMRLNI-AWEZNQCLSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-8,9-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O1[C@@H](COCC1)COC=1C(=C2N(CCC3=C(C(=CC=C23)OC)OC)C(C=1)=O)C AYHBSEIGOMRLNI-AWEZNQCLSA-N 0.000 description 1
- KPAXEJSVQHMXCE-AWEZNQCLSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-8,9-dimethoxy-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O1[C@@H](COCC1)COC=1C=C2N(CCC3=C(C(=CC=C23)OC)OC)C(C=1)=O KPAXEJSVQHMXCE-AWEZNQCLSA-N 0.000 description 1
- VBKDMAIBHHVZBS-ZDUSSCGKSA-N 2-[[(2S)-1,4-dioxan-2-yl]methoxy]-8-hydroxy-9-methoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound O1[C@@H](COCC1)COC=1C(=C2N(CCC3=C(C(=CC=C23)OC)O)C(C=1)=O)C VBKDMAIBHHVZBS-ZDUSSCGKSA-N 0.000 description 1
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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| GBGB1718838.4A GB201718838D0 (en) | 2017-11-15 | 2017-11-15 | Compounds and pharmaceutical compositions thereof for use in the treatment of fibrotic diseases |
| GBGB1817346.8A GB201817346D0 (en) | 2018-10-25 | 2018-10-25 | Compounds and pharmaceutical compositions thereof for use in the treatment of diseases |
| GB1817346.8 | 2018-10-25 | ||
| PCT/EP2018/081457 WO2019096944A1 (en) | 2017-11-15 | 2018-11-15 | Compounds and pharmaceutical compositions thereof for use in the treatment of fibrotic diseases |
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| WO2021123394A1 (en) | 2019-12-20 | 2021-06-24 | University Of Copenhagen | G protein-coupled receptor modulators and a pharmaceutical composition |
| WO2022112186A1 (en) | 2020-11-24 | 2022-06-02 | Galapagos Nv | Compound for use in and methods of treatment of fibrotic diseases |
| JP2024506858A (ja) | 2021-02-02 | 2024-02-15 | リミナル・バイオサイエンシーズ・リミテッド | Ｇｐｒ８４アンタゴニストおよびその使用 |
| WO2022194267A1 (zh) * | 2021-03-18 | 2022-09-22 | 武汉人福创新药物研发中心有限公司 | 一种gpr84拮抗剂及其制备方法和用途 |
| WO2022218372A1 (zh) * | 2021-04-14 | 2022-10-20 | 武汉人福创新药物研发中心有限公司 | 一种二氢嘧啶并异喹啉酮类衍生物及用途 |
| US20250066335A1 (en) | 2021-06-18 | 2025-02-27 | University Of Copenhagen | Polysubstituted 4-hydroxypyridine and 4-hydroxyquinoline derivatives as gpr84 antagonists |
| JP7705966B2 (ja) * | 2021-06-21 | 2025-07-10 | 武漢人福創新薬物研発中心有限公司 | Ｇｐｒ８４アンタゴニストとしての三環式化合物 |
| WO2024220480A2 (en) * | 2023-04-17 | 2024-10-24 | The Board Of Trustees Of The Leland Stanford Junior University | Method for detecting innate immune action in vivo using gpr84-pet |
| CN119591596B (zh) * | 2024-12-04 | 2025-10-17 | 沈阳药科大学 | 4,5-二氢-3H-吡咯并[2,3-c]喹啉-4-酮衍生物及其应用 |
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| AR089284A1 (es) * | 2011-12-22 | 2014-08-13 | Galapagos Nv | Dihidropirimidinoisoquinolinonas y composiciones farmaceuticas de las mismas para el tratamiento de trastornos inflamatorios |
| EP2935262B1 (en) | 2012-12-20 | 2017-03-15 | Galapagos NV | Novel dihydropyrimidinoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders (gpr84 antagonists) |
| SI2970255T1 (sl) | 2013-03-14 | 2017-12-29 | Galapagos Nv | Spojine in farmacevtski sestavki le-teh za zdravljenje vnetnih motenj |
| TWI742541B (zh) * | 2013-03-15 | 2021-10-11 | 英商邊緣生物科技有限公司 | 用於治療肺纖維化、肝纖維化、皮膚纖維化及心臟纖維化之經取代之芳族化合物 |
| GB201411241D0 (en) * | 2014-06-25 | 2014-08-06 | Galapagos Nv | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| GB201506894D0 (en) * | 2015-04-23 | 2015-06-10 | Galapagos Nv | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| GB201603745D0 (en) | 2016-03-04 | 2016-04-20 | Galapagos Nv | Novel compounds and pharmaceutical compositions thereof for the treatment of fibrosis |
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2018
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- 2018-11-15 MA MA050905A patent/MA50905A/fr unknown
- 2018-11-15 AU AU2018367193A patent/AU2018367193A1/en not_active Abandoned
- 2018-11-15 KR KR1020207016903A patent/KR20200088844A/ko not_active Ceased
- 2018-11-15 RU RU2020119415A patent/RU2020119415A/ru unknown
- 2018-11-15 MX MX2020004810A patent/MX2020004810A/es unknown
- 2018-11-15 EP EP23150594.2A patent/EP4186507A1/en not_active Withdrawn
- 2018-11-15 CA CA3082742A patent/CA3082742A1/en active Pending
- 2018-11-15 US US16/764,489 patent/US20210106582A1/en not_active Abandoned
- 2018-11-15 EP EP18822268.1A patent/EP3710004A1/en not_active Withdrawn
- 2018-11-15 JP JP2020526530A patent/JP2021502987A/ja active Pending
- 2018-11-15 BR BR112020008425-5A patent/BR112020008425A2/pt not_active IP Right Cessation
- 2018-11-15 WO PCT/EP2018/081457 patent/WO2019096944A1/en not_active Ceased
- 2018-11-15 SG SG11202004408YA patent/SG11202004408YA/en unknown
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2020
- 2020-05-11 IL IL274578A patent/IL274578A/en unknown
- 2020-05-12 PH PH12020550616A patent/PH12020550616A1/en unknown
- 2020-05-14 CO CONC2020/0005919A patent/CO2020005919A2/es unknown
-
2022
- 2022-11-04 US US17/981,220 patent/US20230241068A1/en not_active Abandoned
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