JP2015531401A - イミダゾピラジノン骨格を有するｐｄｅ９ｉ - Google Patents
イミダゾピラジノン骨格を有するｐｄｅ９ｉ Download PDFInfo
- Publication number
- JP2015531401A JP2015531401A JP2015535994A JP2015535994A JP2015531401A JP 2015531401 A JP2015531401 A JP 2015531401A JP 2015535994 A JP2015535994 A JP 2015535994A JP 2015535994 A JP2015535994 A JP 2015535994A JP 2015531401 A JP2015531401 A JP 2015531401A
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- JP
- Japan
- Prior art keywords
- imidazo
- pyrazin
- methyl
- azetidin
- fluorophenyl
- 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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- MPWOBEOETVOESI-UHFFFAOYSA-N imidazo[4,5-b]pyrazin-2-one Chemical group N1=CC=NC2=NC(=O)N=C21 MPWOBEOETVOESI-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 239000003937 drug carrier Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 6
- -1 8-oxo-3-phenyl-7H-imidazo [1,5-A] pyrazin-6-yl Chemical group 0.000 claims description 65
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims description 15
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 238000007363 ring formation reaction Methods 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 208000028017 Psychotic disease Diseases 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 241000218236 Cannabis Species 0.000 claims description 7
- 208000036626 Mental retardation Diseases 0.000 claims description 7
- 230000007000 age related cognitive decline Effects 0.000 claims description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 7
- 229960003920 cocaine Drugs 0.000 claims description 7
- 239000000380 hallucinogen Substances 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 6
- 229940025084 amphetamine Drugs 0.000 claims description 6
- 229940005483 opioid analgesics Drugs 0.000 claims description 6
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 claims description 6
- 229950010883 phencyclidine Drugs 0.000 claims description 6
- 208000011963 Substance-induced psychotic disease Diseases 0.000 claims description 5
- 231100000393 Substance-induced psychotic disorder Toxicity 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- UIIQLHYXQBZHDU-UHFFFAOYSA-N 3-phenyl-6-[(3-phenylazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1CN(C1)CC1C1=CC=CC=C1 UIIQLHYXQBZHDU-UHFFFAOYSA-N 0.000 claims description 2
- ZLOQDIDEFDRYEQ-UHFFFAOYSA-N 3-phenyl-6-[(3-pyrazin-2-yloxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1CN(C1)CC1OC1=CN=CC=N1 ZLOQDIDEFDRYEQ-UHFFFAOYSA-N 0.000 claims description 2
- UJWXNBFXBBWNBN-UHFFFAOYSA-N 3-phenyl-6-[(3-pyrimidin-2-yloxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1CN(C1)CC1OC1=NC=CC=N1 UJWXNBFXBBWNBN-UHFFFAOYSA-N 0.000 claims description 2
- OZWPMNOQMHSJRL-UHFFFAOYSA-N 3-phenyl-6-[(3-quinoxalin-2-yloxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound N=1C=C2C(=O)NC(CN3CC(C3)OC=3N=C4C=CC=CC4=NC=3)=CN2C=1C1=CC=CC=C1 OZWPMNOQMHSJRL-UHFFFAOYSA-N 0.000 claims description 2
- OLZQZZXWANRKEL-UHFFFAOYSA-N 3-phenyl-6-[1-(3-phenylazetidin-1-yl)ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1C1=CC=CC=C1 OLZQZZXWANRKEL-UHFFFAOYSA-N 0.000 claims description 2
- DWJFOZLYWSESSK-UHFFFAOYSA-N 3-phenyl-6-[1-(3-pyrimidin-2-yloxyazetidin-1-yl)ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=NC=CC=N1 DWJFOZLYWSESSK-UHFFFAOYSA-N 0.000 claims description 2
- YDZCIMPTHKZBJC-UHFFFAOYSA-N 6-(1-benzyl-4-methylpyrrolidin-3-yl)-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C(C)CN1CC1=CC=CC=C1 YDZCIMPTHKZBJC-UHFFFAOYSA-N 0.000 claims description 2
- QVLJPVCBNMVOLX-UHFFFAOYSA-N 6-[(3-anilinopyrrolidin-1-yl)methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1CN(C1)CCC1NC1=CC=CC=C1 QVLJPVCBNMVOLX-UHFFFAOYSA-N 0.000 claims description 2
- UWMJSOJFERDASH-UHFFFAOYSA-N 6-[(3-methoxyazetidin-1-yl)methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(OC)CN1CC(NC1=O)=CN2C1=CN=C2C1=CC=CC=C1 UWMJSOJFERDASH-UHFFFAOYSA-N 0.000 claims description 2
- MNFIXJUASSBZOW-UHFFFAOYSA-N 6-[1-(3-methoxyazetidin-1-yl)ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(OC)CN1C(C)C(NC1=O)=CN2C1=CN=C2C1=CC=CC=C1 MNFIXJUASSBZOW-UHFFFAOYSA-N 0.000 claims description 2
- WMIPWRFZOVGSAJ-UHFFFAOYSA-N 6-[1-(3-phenoxyazetidin-1-yl)ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=CC=C1 WMIPWRFZOVGSAJ-UHFFFAOYSA-N 0.000 claims description 2
- KYRKGOCWXBDKBD-UHFFFAOYSA-N 6-[1-[3-(2-fluorophenoxy)azetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=CC=C1F KYRKGOCWXBDKBD-UHFFFAOYSA-N 0.000 claims description 2
- YMFXDBVYLGTEJF-UHFFFAOYSA-N 6-[1-[3-(3-fluorophenoxy)azetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=CC(F)=C1 YMFXDBVYLGTEJF-UHFFFAOYSA-N 0.000 claims description 2
- BYUYQURHJNXKRJ-UHFFFAOYSA-N 6-[1-[3-(4-ethylphenyl)azetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(CC)=CC=C1C1CN(C(C)C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C1 BYUYQURHJNXKRJ-UHFFFAOYSA-N 0.000 claims description 2
- BGGBTQOCEKKJHN-UHFFFAOYSA-N 6-[1-[3-(4-fluorophenoxy)azetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=C(F)C=C1 BGGBTQOCEKKJHN-UHFFFAOYSA-N 0.000 claims description 2
- FKKWWRNYEOOBSX-UHFFFAOYSA-N 6-[1-[3-(4-fluorophenyl)azetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1C1=CC=C(F)C=C1 FKKWWRNYEOOBSX-UHFFFAOYSA-N 0.000 claims description 2
- BOPIZTALPMZROL-UHFFFAOYSA-N 6-[1-[3-(6-fluoropyridin-2-yl)oxyazetidin-1-yl]ethyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=CC(F)=N1 BOPIZTALPMZROL-UHFFFAOYSA-N 0.000 claims description 2
- DXOVFJHHONEJOL-UHFFFAOYSA-N 6-[[3-(2-fluorophenoxy)azetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound FC1=CC=CC=C1OC1CN(CC=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C1 DXOVFJHHONEJOL-UHFFFAOYSA-N 0.000 claims description 2
- OMKMXPNRMOBLJW-UHFFFAOYSA-N 6-[[3-(3-fluorophenoxy)azetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound FC1=CC=CC(OC2CN(CC=3NC(=O)C4=CN=C(N4C=3)C=3C=CC=CC=3)C2)=C1 OMKMXPNRMOBLJW-UHFFFAOYSA-N 0.000 claims description 2
- BCFBUHSRTSXNFB-UHFFFAOYSA-N 6-[[3-(4,6-dimethylpyrimidin-2-yl)oxyazetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound CC1=CC(C)=NC(OC2CN(CC=3NC(=O)C4=CN=C(N4C=3)C=3C=CC=CC=3)C2)=N1 BCFBUHSRTSXNFB-UHFFFAOYSA-N 0.000 claims description 2
- OAMBWTBJNZOALP-UHFFFAOYSA-N 6-[[3-(4-ethylphenyl)azetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(CC)=CC=C1C1CN(CC=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C1 OAMBWTBJNZOALP-UHFFFAOYSA-N 0.000 claims description 2
- CPWSTVGPJSYNMA-UHFFFAOYSA-N 6-[[3-(4-fluorophenoxy)azetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1OC1CN(CC=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C1 CPWSTVGPJSYNMA-UHFFFAOYSA-N 0.000 claims description 2
- MAKIYAKALMRMOD-UHFFFAOYSA-N 6-[[3-(6-fluoropyridin-2-yl)oxyazetidin-1-yl]methyl]-3-phenyl-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound FC1=CC=CC(OC2CN(CC=3NC(=O)C4=CN=C(N4C=3)C=3C=CC=CC=3)C2)=N1 MAKIYAKALMRMOD-UHFFFAOYSA-N 0.000 claims description 2
- DMIUQICEZBGJHR-UHFFFAOYSA-N methyl 1-benzyl-4-(8-oxo-3-phenyl-7h-imidazo[1,5-a]pyrazin-6-yl)pyrrolidine-3-carboxylate Chemical compound C1C(C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC=CC=2)C(C(=O)OC)CN1CC1=CC=CC=C1 DMIUQICEZBGJHR-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 2
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
- FKZBSXUJAGAAGL-UHFFFAOYSA-N 1-bromo-3-(4-chlorophenyl)-6-[1-[(4-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=C(Br)N=C(N3C=2)C=2C=CC(Cl)=CC=2)C(C)CN1CC1=CC=C(F)C=C1 FKZBSXUJAGAAGL-UHFFFAOYSA-N 0.000 claims 1
- LYDLONHBBHMLKV-UHFFFAOYSA-N 1-bromo-3-(4-fluorophenyl)-6-[1-[(4-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=C(Br)N=C(N3C=2)C=2C=CC(F)=CC=2)C(C)CN1CC1=CC=C(F)C=C1 LYDLONHBBHMLKV-UHFFFAOYSA-N 0.000 claims 1
- WZEBNPXEWQABBM-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-6-[[3-(4-methoxyphenyl)azetidin-1-yl]methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(OC)=CC=C1C1CN(CC=2NC(=O)C3=CN=C(N3C=2)C=2C=C(F)C=C(F)C=2)C1 WZEBNPXEWQABBM-UHFFFAOYSA-N 0.000 claims 1
- QWXPAEULRAXJME-UHFFFAOYSA-N 3-(4,4-difluorocyclohexyl)-6-[(3-methoxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(OC)CN1CC(NC1=O)=CN2C1=CN=C2C1CCC(F)(F)CC1 QWXPAEULRAXJME-UHFFFAOYSA-N 0.000 claims 1
- XEVNPWFTIMDURN-UHFFFAOYSA-N 3-(4,4-difluorocyclohexyl)-6-[[3-(4-methoxyphenyl)azetidin-1-yl]methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(OC)=CC=C1C1CN(CC=2NC(=O)C3=CN=C(N3C=2)C2CCC(F)(F)CC2)C1 XEVNPWFTIMDURN-UHFFFAOYSA-N 0.000 claims 1
- QUVZKCAAXZEUKT-UHFFFAOYSA-N 3-(4-chlorophenyl)-6-[1-[(4-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC(Cl)=CC=2)C(C)CN1CC1=CC=C(F)C=C1 QUVZKCAAXZEUKT-UHFFFAOYSA-N 0.000 claims 1
- FXDZYGQOMMBTKL-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-phenoxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OC=3C=CC=CC=3)=CN12 FXDZYGQOMMBTKL-UHFFFAOYSA-N 0.000 claims 1
- FGZIMOPQPLAICG-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-phenoxypyrrolidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(CC3)OC=3C=CC=CC=3)=CN12 FGZIMOPQPLAICG-UHFFFAOYSA-N 0.000 claims 1
- YRNHKKWWMGNSJH-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-phenylmethoxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OCC=3C=CC=CC=3)=CN12 YRNHKKWWMGNSJH-UHFFFAOYSA-N 0.000 claims 1
- BJRLUBFRQQIWDK-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-pyrazin-2-yloxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OC=3N=CC=NC=3)=CN12 BJRLUBFRQQIWDK-UHFFFAOYSA-N 0.000 claims 1
- OPPJESMUQLKXLM-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-pyridin-4-yloxyazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OC=3C=CN=CC=3)=CN12 OPPJESMUQLKXLM-UHFFFAOYSA-N 0.000 claims 1
- FQTKUALMFWAFOT-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(3-pyrimidin-2-ylazetidin-1-yl)methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)C=3N=CC=CN=3)=CN12 FQTKUALMFWAFOT-UHFFFAOYSA-N 0.000 claims 1
- KZXQDNGEOOWVOT-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[1-(3-methoxyazetidin-1-yl)ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(OC)CN1C(C)C(NC1=O)=CN2C1=CN=C2C1=CC=C(F)C=C1 KZXQDNGEOOWVOT-UHFFFAOYSA-N 0.000 claims 1
- VURKBBXXUCMNNY-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[1-(3-propan-2-yloxyazetidin-1-yl)ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(OC(C)C)CN1C(C)C(NC1=O)=CN2C1=CN=C2C1=CC=C(F)C=C1 VURKBBXXUCMNNY-UHFFFAOYSA-N 0.000 claims 1
- IXXFEEXROAIYKE-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[1-[(4-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC(F)=CC=2)C(C)CN1CC1=CC=C(F)C=C1 IXXFEEXROAIYKE-UHFFFAOYSA-N 0.000 claims 1
- DECWKGNPLGHKNM-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[1-[3-(4-methoxyphenyl)azetidin-1-yl]ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(OC)=CC=C1C1CN(C(C)C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC(F)=CC=2)C1 DECWKGNPLGHKNM-UHFFFAOYSA-N 0.000 claims 1
- QAWRXXWLFINXRI-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[1-[3-[4-(trifluoromethoxy)phenoxy]azetidin-1-yl]ethyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C=1N2C(C=3C=CC(F)=CC=3)=NC=C2C(=O)NC=1C(C)N(C1)CC1OC1=CC=C(OC(F)(F)F)C=C1 QAWRXXWLFINXRI-UHFFFAOYSA-N 0.000 claims 1
- KQUHRFKFEIWQQX-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[4-methyl-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1C(C=2NC(=O)C3=CN=C(N3C=2)C=2C=CC(F)=CC=2)C(C)CN1CC1=CC=CC=N1 KQUHRFKFEIWQQX-UHFFFAOYSA-N 0.000 claims 1
- RQTYTKFUFIQXRT-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[[3-(4-methoxyphenyl)azetidin-1-yl]methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(OC)=CC=C1C1CN(CC=2NC(=O)C3=CN=C(N3C=2)C=2C=CC(F)=CC=2)C1 RQTYTKFUFIQXRT-UHFFFAOYSA-N 0.000 claims 1
- SNADRBGYEUKACC-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[[3-(6-fluoropyridin-2-yl)oxyazetidin-1-yl]methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OC=3N=C(F)C=CC=3)=CN12 SNADRBGYEUKACC-UHFFFAOYSA-N 0.000 claims 1
- OQOLKOFSTBTOOE-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[[3-[3-(trifluoromethyl)phenoxy]azetidin-1-yl]methyl]-7h-imidazo[1,5-a]pyrazin-8-one Chemical compound C1=CC(F)=CC=C1C1=NC=C2C(=O)NC(CN3CC(C3)OC=3C=C(C=CC=3)C(F)(F)F)=CN12 OQOLKOFSTBTOOE-UHFFFAOYSA-N 0.000 claims 1
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Landscapes
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| CN2011001692 | 2011-10-10 | ||
| PCT/EP2012/069936 WO2013053690A1 (en) | 2011-10-10 | 2012-10-09 | Pde9i with imidazo pyrazinone backbone |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019534324A (ja) * | 2016-10-18 | 2019-11-28 | ハー・ルンドベック・アクチエゼルスカベット | Ｐｄｅ１阻害剤としてのイミダゾピラジノン、ピラゾロピリミジノンおよびピラゾロピリジノン |
| JP2019536762A (ja) * | 2016-10-28 | 2019-12-19 | ハー・ルンドベック・アクチエゼルスカベット | 精神疾患及び／又は認知障害の治療のためのイミダゾピラジノンを含む併用療法 |
| JP2020500841A (ja) * | 2016-10-28 | 2020-01-16 | ハー・ルンドベック・アクチエゼルスカベット | イミダゾピラジノンの投与を含む併用療法 |
| KR20200016891A (ko) * | 2017-05-26 | 2020-02-17 | 이마라 인크. | Pde9 억제제의 제조 방법 및 사용 방법 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX381326B (es) * | 2011-10-10 | 2025-03-12 | H Lundbeck As | Derivados de 7h-imidazo[1-5-a]pirazin-8-ona como inhibidores de la fosfodiesterasa 9(pde9); y el uso de los mismos en el tratamiento de trastornos neurodegenerativos |
| US9527835B2 (en) | 2014-02-13 | 2016-12-27 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| WO2015123424A1 (en) | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| LT3105218T (lt) | 2014-02-13 | 2019-12-10 | Incyte Corp | Ciklopropilaminai kaip lsd1 inhibitoriai |
| EP3392244A1 (en) | 2014-02-13 | 2018-10-24 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| WO2016007722A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| WO2016007731A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Imidazopyridines and imidazopyrazines as lsd1 inhibitors |
| US9758523B2 (en) | 2014-07-10 | 2017-09-12 | Incyte Corporation | Triazolopyridines and triazolopyrazines as LSD1 inhibitors |
| WO2016007736A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Imidazopyrazines as lsd1 inhibitors |
| TW201629064A (zh) | 2014-10-10 | 2016-08-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之三唑並吡酮 |
| EA201792205A1 (ru) | 2015-04-03 | 2018-02-28 | Инсайт Корпорейшн | Гетероциклические соединения как ингибиторы lsd1 |
| JO3627B1 (ar) * | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| CA2990521C (en) * | 2015-07-07 | 2023-10-10 | H. Lundbeck A/S | Pde9 inhibitors with imidazo triazinone backbone and imidazo pyrazinone backbone for treatment of peripheral diseases |
| TW201717948A (zh) * | 2015-08-10 | 2017-06-01 | Ｈ 朗德貝克公司 | 包括給予２－胺基－３，５，５－三氟－３，４，５，６－四氫吡啶的聯合治療 |
| DK3334709T3 (da) | 2015-08-12 | 2025-02-03 | Incyte Holdings Corp | Salte af en lsd1-hæmmer |
| SMT202000152T1 (it) * | 2015-11-09 | 2020-05-08 | Astrazeneca Ab | Derivati di diidroimidazopirazinone utili nel trattamento di cancro |
| TWI729109B (zh) | 2016-04-12 | 2021-06-01 | 丹麥商Ｈ 朗德貝克公司 | 作爲PDE1抑制劑的1,5-二氫-4H-吡唑并[3,4-d]嘧啶-4-酮和1,5-二氫-4H-吡唑并[4,3-c]吡啶-4-酮 |
| CA3021678A1 (en) | 2016-04-22 | 2017-10-26 | Incyte Corporation | Formulations of an lsd1 inhibitor |
| IL295973A (en) | 2016-07-06 | 2022-10-01 | H Lundbeck As | pde9 inhibitors for the treatment of peripheral diseases |
| AU2018223192A1 (en) * | 2017-02-27 | 2019-06-20 | Janssen Pharmaceutica Nv | [1,2,4]-triazolo [1,5-a]-pyrimidinyl derivatives substituted with piperidine, morpholine or piperazine as OGA inhibitors |
| JP2020523309A (ja) | 2017-06-08 | 2020-08-06 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | ピラゾロピリミジンｐｄｅ９インヒビター |
| WO2019101511A1 (en) | 2017-11-23 | 2019-05-31 | Basf Se | Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi |
| BR112020024019A2 (pt) | 2018-05-25 | 2021-02-23 | Imara Inc. | monoidrato e formas cristalinas de 6-[(3s,4s)-4-metil-1-(pirimidin-2-ilmetil)pirrolidin-3-il]-3-tetra-hidropiran-4-il-7h-imidazo[1,5-a]pirazin-8-ona |
| US20210115040A1 (en) * | 2018-06-20 | 2021-04-22 | Janssen Pharmaceutica Nv | Oga inhibitor compounds |
| US10968200B2 (en) | 2018-08-31 | 2021-04-06 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| KR20250108770A (ko) | 2018-08-31 | 2025-07-15 | 카듀리온 파마슈티칼스, 인크. | 겸상 세포 질환의 치료를 위한 pde9 억제제 |
| WO2020206336A1 (en) * | 2019-04-05 | 2020-10-08 | Imara Inc. | Pde9 inhibitors for treating sickle cell disease |
| CN114072151A (zh) * | 2019-05-07 | 2022-02-18 | 伊马拉公司 | 用于治疗地中海贫血的pde9抑制剂 |
| WO2022036111A1 (en) * | 2020-08-13 | 2022-02-17 | Imara Inc. | Methods and compositions for treating sickle cell disease |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005511575A (ja) * | 2001-11-02 | 2005-04-28 | ファイザー インコーポレイテッド | 心臓血管障害を治療するためのｐｄｅ９阻害剤 |
| JP2010526863A (ja) * | 2007-05-11 | 2010-08-05 | ファイザー・インク | アミノ複素環式化合物 |
| WO2012040230A1 (en) * | 2010-09-20 | 2012-03-29 | Envivo Pharmaceuticals, Inc. | Imidazotriazinone compounds |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU227841B1 (en) | 1997-11-12 | 2012-05-02 | Bayer Pharma AG | 2-phenyl substituted imidazotriazinones, process for their preparation and pharmaceutical compositions thereof |
| KR20010101603A (ko) | 1999-01-20 | 2001-11-14 | 노왈드 | 이미다조[1,5-ａ]-피리도[3,2-ｅ]-피라지논의 약제로서의용도 |
| KR20040053210A (ko) | 2001-11-02 | 2004-06-23 | 화이자 프로덕츠 인크. | Ｐｄｅ9 억제제를 사용한 인슐린 저항 증후군 및 2형당뇨병의 치료 |
| GB2388111A (en) | 2002-05-01 | 2003-11-05 | Bayer Ag | Novel imidazotriazinone compounds |
| US20040220186A1 (en) | 2003-04-30 | 2004-11-04 | Pfizer Inc. | PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease |
| BRPI0416118A (pt) | 2003-10-31 | 2007-01-02 | Pfizer Prod Inc | inibição da fosfodiesterase 9 como tratamento para estados relacionados com a obesidade |
| EP1928237A4 (en) | 2005-09-02 | 2011-03-09 | Abbott Lab | NEW HETEROCYCLES BASED ON IMIDAZO |
| TW200815436A (en) * | 2006-05-30 | 2008-04-01 | Elbion Ag | 4-amino-pyrido[3,2-e]pyrazines, their use as inhibitors of phosphodiesterase 10, and processes for preparing them |
| WO2008029589A1 (en) | 2006-09-08 | 2008-03-13 | Tokuyama Corporation | Method and equipment for producing group-iii nitride |
| WO2008072779A1 (ja) | 2006-12-13 | 2008-06-19 | Aska Pharmaceutical Co., Ltd. | キノキサリン誘導体 |
| AU2007332439A1 (en) | 2006-12-13 | 2008-06-19 | Aska Pharmaceutical Co., Ltd. | Therapeutic agent for urinary tract disease |
| DE102007032349A1 (de) | 2007-07-11 | 2009-01-15 | Bayer Healthcare Ag | Imidazo-, Pyrazolopyrazine und Imidazotriazine und ihre Verwendung |
| TWI404721B (zh) | 2009-01-26 | 2013-08-11 | Pfizer | 胺基－雜環化合物 |
| WO2011028820A1 (en) | 2009-09-02 | 2011-03-10 | Concert Pharmaceuticals, Inc. | Substituted derivatives of bicyclic [4.3.0] heteroaryl compounds |
| CN103930423B (zh) | 2011-10-07 | 2015-09-16 | 卫材Rd管理有限公司 | 吡唑并喹啉衍生物 |
| MX381326B (es) * | 2011-10-10 | 2025-03-12 | H Lundbeck As | Derivados de 7h-imidazo[1-5-a]pirazin-8-ona como inhibidores de la fosfodiesterasa 9(pde9); y el uso de los mismos en el tratamiento de trastornos neurodegenerativos |
| EP2807163B1 (en) | 2012-01-26 | 2017-03-22 | H. Lundbeck A/S | Pde9 inhibitors with imidazo triazinone backbone |
| EP2828262A4 (en) | 2012-03-19 | 2015-09-23 | Forum Pharmaceuticals Inc | IMIDAZOTRIAZINONVERBINDUNGEN |
-
2012
- 2012-10-09 MX MX2019014982A patent/MX381326B/es unknown
- 2012-10-09 CN CN201710247417.1A patent/CN106905324B/zh active Active
- 2012-10-09 CN CN201280076285.6A patent/CN104703987B/zh active Active
- 2012-10-09 EP EP16185105.0A patent/EP3121178B1/en active Active
- 2012-10-09 BR BR112015007731-5A patent/BR112015007731B1/pt active IP Right Grant
- 2012-10-09 MX MX2015004422A patent/MX370433B/es active IP Right Grant
- 2012-10-09 HK HK15111740.3A patent/HK1211023A1/xx unknown
- 2012-10-09 CA CA2886885A patent/CA2886885C/en active Active
- 2012-10-09 WO PCT/EP2012/069936 patent/WO2013053690A1/en not_active Ceased
- 2012-10-09 MA MA37958A patent/MA37958B1/fr unknown
- 2012-10-09 IN IN2829DEN2015 patent/IN2015DN02829A/en unknown
- 2012-10-09 SG SG11201502728WA patent/SG11201502728WA/en unknown
- 2012-10-09 JP JP2015535994A patent/JP2015531401A/ja active Pending
- 2012-10-09 US US14/434,308 patent/US9643970B2/en active Active
- 2012-10-09 EP EP12772769.1A patent/EP2906562B1/en active Active
- 2012-10-09 AU AU2012323085A patent/AU2012323085B2/en active Active
-
2015
- 2015-03-16 TN TNP2015000100A patent/TN2015000100A1/fr unknown
- 2015-03-19 IL IL237836A patent/IL237836A/en active IP Right Grant
-
2017
- 2017-03-08 US US15/452,827 patent/US9993477B2/en active Active
- 2017-03-20 AU AU2017201873A patent/AU2017201873C1/en active Active
- 2017-07-12 IL IL253448A patent/IL253448A0/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005511575A (ja) * | 2001-11-02 | 2005-04-28 | ファイザー インコーポレイテッド | 心臓血管障害を治療するためのｐｄｅ９阻害剤 |
| JP2010526863A (ja) * | 2007-05-11 | 2010-08-05 | ファイザー・インク | アミノ複素環式化合物 |
| WO2012040230A1 (en) * | 2010-09-20 | 2012-03-29 | Envivo Pharmaceuticals, Inc. | Imidazotriazinone compounds |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019534324A (ja) * | 2016-10-18 | 2019-11-28 | ハー・ルンドベック・アクチエゼルスカベット | Ｐｄｅ１阻害剤としてのイミダゾピラジノン、ピラゾロピリミジノンおよびピラゾロピリジノン |
| JP7112413B2 (ja) | 2016-10-18 | 2022-08-03 | ハー・ルンドベック・アクチエゼルスカベット | Ｐｄｅ１阻害剤としてのイミダゾピラジノン、ピラゾロピリミジノンおよびピラゾロピリジノン |
| JP2019536762A (ja) * | 2016-10-28 | 2019-12-19 | ハー・ルンドベック・アクチエゼルスカベット | 精神疾患及び／又は認知障害の治療のためのイミダゾピラジノンを含む併用療法 |
| JP2020500841A (ja) * | 2016-10-28 | 2020-01-16 | ハー・ルンドベック・アクチエゼルスカベット | イミダゾピラジノンの投与を含む併用療法 |
| KR20200016891A (ko) * | 2017-05-26 | 2020-02-17 | 이마라 인크. | Pde9 억제제의 제조 방법 및 사용 방법 |
| JP2020527535A (ja) * | 2017-05-26 | 2020-09-10 | イマラ インク． | Ｐｄｅ９阻害剤を製造および使用する方法 |
| KR102627975B1 (ko) | 2017-05-26 | 2024-01-19 | 이마라 인크. | Pde9 억제제의 제조 방법 및 사용 방법 |
| US11999741B2 (en) | 2017-05-26 | 2024-06-04 | Cardurion Pharmaceuticals, Inc. | Process for the synthesis of 6-((3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-3-(tetrahydropyran-4-yl-7H-imidazo[1,5-a]pyrazin-8-one |
| JP7609518B2 (ja) | 2017-05-26 | 2025-01-07 | カーデュリオン・ファーマシューティカルズ・インコーポレイテッド | Ｐｄｅ９阻害剤を製造および使用する方法 |
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