JP7346441B2 - 置換ピリジン及びピリミジン並びにglun2b受容体調節物質としてのそれらの使用 - Google Patents
置換ピリジン及びピリミジン並びにglun2b受容体調節物質としてのそれらの使用 Download PDFInfo
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- JP7346441B2 JP7346441B2 JP2020554286A JP2020554286A JP7346441B2 JP 7346441 B2 JP7346441 B2 JP 7346441B2 JP 2020554286 A JP2020554286 A JP 2020554286A JP 2020554286 A JP2020554286 A JP 2020554286A JP 7346441 B2 JP7346441 B2 JP 7346441B2
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- Prior art keywords
- phenyl
- fluoro
- trifluoromethoxy
- acetamide
- piperidyl
- Prior art date
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- 108010054200 NR2B NMDA receptor Proteins 0.000 title 1
- 150000003222 pyridines Chemical class 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 536
- -1 CH 2 OH Chemical group 0.000 claims description 331
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 186
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 136
- 125000000217 alkyl group Chemical group 0.000 claims description 132
- 150000003839 salts Chemical class 0.000 claims description 132
- 239000012453 solvate Substances 0.000 claims description 92
- 150000001204 N-oxides Chemical class 0.000 claims description 87
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 81
- 230000000155 isotopic effect Effects 0.000 claims description 80
- 239000002904 solvent Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- 229910052731 fluorine Inorganic materials 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 46
- 208000035475 disorder Diseases 0.000 claims description 46
- 125000001188 haloalkyl group Chemical group 0.000 claims description 44
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 26
- 206010015037 epilepsy Diseases 0.000 claims description 26
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
- 108010038912 Retinoid X Receptors Proteins 0.000 claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 230000001404 mediated effect Effects 0.000 claims description 18
- 208000002193 Pain Diseases 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 12
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- DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims description 9
- ZKARWIMNUTYCHQ-HZPDHXFCSA-N N-[(3R,4R)-3-fluoro-1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound F[C@@H]1CN(CC[C@H]1NC(C)=O)C1=CC(=NC=C1)C1=CC(=C(C=C1)OC(F)(F)F)F ZKARWIMNUTYCHQ-HZPDHXFCSA-N 0.000 claims description 9
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- XJLDYKIEURAVBW-UHFFFAOYSA-N 3-decanone Chemical compound CCCCCCCC(=O)CC XJLDYKIEURAVBW-UHFFFAOYSA-N 0.000 claims description 8
- SHPKMOIOPXYKDQ-ZIAGYGMSSA-N N-[(3R,4R)-1-[6-[3-chloro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]-3-fluoropiperidin-4-yl]acetamide Chemical compound ClC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC=N1)N1C[C@H]([C@@H](CC1)NC(C)=O)F SHPKMOIOPXYKDQ-ZIAGYGMSSA-N 0.000 claims description 8
- GXHJDGZRLYYINV-ZIAGYGMSSA-N N-[(3R,4R)-3-fluoro-1-[6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound F[C@@H]1CN(CC[C@H]1NC(C)=O)C1=NC=NC(=C1)C1=CC(=C(C=C1)OC(F)(F)F)F GXHJDGZRLYYINV-ZIAGYGMSSA-N 0.000 claims description 8
- LYEOIDSQUSCGTE-HUUCEWRRSA-N N-[(3R,4R)-3-fluoro-1-[6-[3-methyl-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound F[C@@H]1CN(CC[C@H]1NC(C)=O)C1=NC=NC(=C1)C1=CC(=C(C=C1)OC(F)(F)F)C LYEOIDSQUSCGTE-HUUCEWRRSA-N 0.000 claims description 8
- GXHJDGZRLYYINV-KGLIPLIRSA-N N-[(3R,4S)-3-fluoro-1-[6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound F[C@@H]1CN(CC[C@@H]1NC(C)=O)C1=NC=NC(=C1)C1=CC(=C(C=C1)OC(F)(F)F)F GXHJDGZRLYYINV-KGLIPLIRSA-N 0.000 claims description 8
- PRVBZDFTFIKYHR-UHFFFAOYSA-N N-[3-[[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]amino]-2-methylpropyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)NCC(CNC(C)=O)C PRVBZDFTFIKYHR-UHFFFAOYSA-N 0.000 claims description 8
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- RGYJALVGNBTJET-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O RGYJALVGNBTJET-UHFFFAOYSA-N 0.000 claims description 7
- CGNHBXMBWGCZBU-UHFFFAOYSA-N N-[1-[6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC=N1)N1CCC(CC1)NC(C)=O CGNHBXMBWGCZBU-UHFFFAOYSA-N 0.000 claims description 7
- VDHUZQZZZTZDKC-UHFFFAOYSA-N N-[1-[6-[3-methyl-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound CC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC=N1)N1CCC(CC1)NC(C)=O VDHUZQZZZTZDKC-UHFFFAOYSA-N 0.000 claims description 7
- WVNKOCRFJRNXMO-UHFFFAOYSA-N 2-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)N1CCC(CC1)CC(=O)N WVNKOCRFJRNXMO-UHFFFAOYSA-N 0.000 claims description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 6
- 206010008748 Chorea Diseases 0.000 claims description 6
- LYXBMZYRQMVQKV-UHFFFAOYSA-N N-[1-[2-(fluoromethyl)-6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FCC1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)C1=CC(=C(C=C1)OC(F)(F)F)F LYXBMZYRQMVQKV-UHFFFAOYSA-N 0.000 claims description 6
- QXNVECOCVVXBEY-UHFFFAOYSA-N N-[1-[2-[3-chloro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound ClC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O QXNVECOCVVXBEY-UHFFFAOYSA-N 0.000 claims description 6
- JLKZSXOJECJKMH-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-(hydroxymethyl)pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)CO JLKZSXOJECJKMH-UHFFFAOYSA-N 0.000 claims description 6
- VNLBXMXSKDVVPR-UHFFFAOYSA-N N-[1-[2-[3-methyl-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound CC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O VNLBXMXSKDVVPR-UHFFFAOYSA-N 0.000 claims description 6
- WFZYMJHCZMEXNM-UHFFFAOYSA-N N-[1-[2-[4-(difluoromethoxy)-3-methylphenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC(OC1=C(C=C(C=C1)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O)C)F WFZYMJHCZMEXNM-UHFFFAOYSA-N 0.000 claims description 6
- KIYYIEMAENLYPX-UHFFFAOYSA-N N-[1-[2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC(OC1=CC=C(C=C1)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O)(F)F KIYYIEMAENLYPX-UHFFFAOYSA-N 0.000 claims description 6
- XOBLXIXOWJGCHC-UHFFFAOYSA-N N-[3-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]oxycyclobutyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)OC1CC(C1)NC(C)=O XOBLXIXOWJGCHC-UHFFFAOYSA-N 0.000 claims description 6
- KGWBZAIGRBUSPI-UHFFFAOYSA-N N-[4-[[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]amino]cyclohexyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)NC1CCC(CC1)NC(C)=O KGWBZAIGRBUSPI-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052801 chlorine Inorganic materials 0.000 claims description 6
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- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
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- AJVLXOBMCOAOTF-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]-3-methylpiperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)N1CC(C(CC1)NC(C)=O)C AJVLXOBMCOAOTF-UHFFFAOYSA-N 0.000 claims description 5
- JEFLRAHMBXWYTH-UHFFFAOYSA-N N-[3-[[6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]amino]-2-methylpropyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC=N1)NCC(CNC(C)=O)C JEFLRAHMBXWYTH-UHFFFAOYSA-N 0.000 claims description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
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- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 4
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 4
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 4
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- HDEPYOIGLFBBCJ-HZPDHXFCSA-N N-[(3R,4R)-3-fluoro-1-[2-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound F[C@@H]1CN(CC[C@H]1NC(C)=O)C1=NC(=NC(=C1)C1=CC=C(C=C1)OC(F)(F)F)C HDEPYOIGLFBBCJ-HZPDHXFCSA-N 0.000 claims description 4
- YNCHYPYARJXMCM-UHFFFAOYSA-N N-[1-[2-[3-(difluoromethoxy)-4-fluorophenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC(OC=1C=C(C=CC=1F)C1=NC=CC(=C1)N1CCC(CC1)NC(C)=O)F YNCHYPYARJXMCM-UHFFFAOYSA-N 0.000 claims description 4
- PHTYVBAIOJGHLC-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-methoxypyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)OC PHTYVBAIOJGHLC-UHFFFAOYSA-N 0.000 claims description 4
- ZGXORXYBQMOKQF-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-methylpyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)C ZGXORXYBQMOKQF-UHFFFAOYSA-N 0.000 claims description 4
- ZPOBDGCZBRWBHD-UHFFFAOYSA-N N-[1-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-oxo-1H-pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)O ZPOBDGCZBRWBHD-UHFFFAOYSA-N 0.000 claims description 4
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- RQAQFMUMIJACHO-UHFFFAOYSA-N N-[1-[2-cyano-6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]piperidin-4-yl]acetamide Chemical compound C(#N)C1=NC(=CC(=C1)N1CCC(CC1)NC(C)=O)C1=CC(=C(C=C1)OC(F)(F)F)F RQAQFMUMIJACHO-UHFFFAOYSA-N 0.000 claims description 4
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- YCEHWRFDAAKIHR-UHFFFAOYSA-N N-[1-[6-[3-chloro-4-(trifluoromethoxy)phenyl]-2-methylpyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound ClC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC(=N1)C)N1CCC(CC1)NC(C)=O YCEHWRFDAAKIHR-UHFFFAOYSA-N 0.000 claims description 4
- JXJTWLGJPUSBJS-UHFFFAOYSA-N N-[1-[6-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-(hydroxymethyl)pyrimidin-4-yl]piperidin-4-yl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC(=N1)CO)N1CCC(CC1)NC(C)=O JXJTWLGJPUSBJS-UHFFFAOYSA-N 0.000 claims description 4
- JOPVQOZDXRALAZ-UHFFFAOYSA-N N-[3-[[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-(hydroxymethyl)pyridin-4-yl]amino]-2-methylpropyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)NCC(CNC(C)=O)C)CO JOPVQOZDXRALAZ-UHFFFAOYSA-N 0.000 claims description 4
- NLQGWSLNGJKVHE-UHFFFAOYSA-N N-[4-[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]cyclohexyl]acetamide Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)C1CCC(CC1)NC(C)=O NLQGWSLNGJKVHE-UHFFFAOYSA-N 0.000 claims description 4
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- UFXLZWXTEZPMHO-UHFFFAOYSA-N N-methyl-1-[6-[4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]pyrrolidine-3-carboxamide Chemical compound CNC(=O)C1CN(CC1)C1=NC=NC(=C1)C1=CC=C(C=C1)OC(F)(F)F UFXLZWXTEZPMHO-UHFFFAOYSA-N 0.000 claims description 4
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- NCTYUZPCPWEGOY-UHFFFAOYSA-N 1-[1-[6-[3-fluoro-4-(trifluoromethoxy)phenyl]pyrimidin-4-yl]piperidin-4-yl]ethanone Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=CC(=NC=N1)N1CCC(CC1)C(C)=O NCTYUZPCPWEGOY-UHFFFAOYSA-N 0.000 claims description 3
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- HCFRYADGHLZUCI-UHFFFAOYSA-N 1-[3-[[[2-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridin-4-yl]amino]methyl]azetidin-1-yl]ethanone Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC=CC(=C1)NCC1CN(C1)C(C)=O HCFRYADGHLZUCI-UHFFFAOYSA-N 0.000 claims description 3
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- LSZHECLEXYNNTQ-UHFFFAOYSA-N tert-butyl N-[3-[[2-[3-fluoro-4-(trifluoromethoxy)phenyl]-6-(hydroxymethyl)pyridin-4-yl]amino]-2-methylpropyl]carbamate Chemical compound FC=1C=C(C=CC=1OC(F)(F)F)C1=NC(=CC(=C1)NCC(CNC(OC(C)(C)C)=O)C)CO LSZHECLEXYNNTQ-UHFFFAOYSA-N 0.000 description 1
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- MSCLVLGMLLYXFV-UHFFFAOYSA-N tert-butyl n-(3-aminobutyl)carbamate Chemical compound CC(N)CCNC(=O)OC(C)(C)C MSCLVLGMLLYXFV-UHFFFAOYSA-N 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- JOFFSNZHLGGAJC-UHFFFAOYSA-N tert-butyl n-(4-aminobutan-2-yl)carbamate Chemical compound NCCC(C)NC(=O)OC(C)(C)C JOFFSNZHLGGAJC-UHFFFAOYSA-N 0.000 description 1
- ZFQWJXFJJZUVPI-UHFFFAOYSA-N tert-butyl n-(4-aminobutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCN ZFQWJXFJJZUVPI-UHFFFAOYSA-N 0.000 description 1
- KHPQHXGYYXYTDN-UHFFFAOYSA-N tert-butyl n-(piperidin-3-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCCNC1 KHPQHXGYYXYTDN-UHFFFAOYSA-N 0.000 description 1
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- YIMSPDZAVBIXRT-UHFFFAOYSA-N tert-butyl n-[3-(methylamino)propyl]carbamate Chemical compound CNCCCNC(=O)OC(C)(C)C YIMSPDZAVBIXRT-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
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Classifications
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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| US201862652458P | 2018-04-04 | 2018-04-04 | |
| US62/652,458 | 2018-04-04 | ||
| PCT/IB2019/052731 WO2019193516A2 (en) | 2018-04-04 | 2019-04-03 | Substituted pyridine and pyrimidines and their use as glun2b receptor modulators |
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| JP2021520381A JP2021520381A (ja) | 2021-08-19 |
| JP2021520381A5 JP2021520381A5 (https=) | 2022-04-06 |
| JP7346441B2 true JP7346441B2 (ja) | 2023-09-19 |
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| WO (1) | WO2019193516A2 (https=) |
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| US10071988B2 (en) | 2016-02-10 | 2018-09-11 | Janssen Pharmaceutica Nv | Substituted 1,2,3-triazoles as NR2B-selective NMDA modulators |
| TW201819376A (zh) | 2016-10-06 | 2018-06-01 | 比利時商健生藥品公司 | 經取代之1H-咪唑並[4,5-b]吡啶-2(3H)-酮及其作為GLUN2B受體調節劑之用途 |
| MX2021015511A (es) | 2019-06-14 | 2022-01-31 | Janssen Pharmaceutica Nv | Carbamatos de pirazina y sus usos como moduladores del receptor glun2b. |
| CA3143103A1 (en) | 2019-06-14 | 2020-12-17 | Janssen Pharmaceutica Nv | Pyridine carbamates and their use as glun2b receptor modulators |
| AU2020293642A1 (en) | 2019-06-14 | 2022-01-20 | Janssen Pharmaceutica Nv | Substituted pyrazolo[4,3-b]pyridines and their use as GluN2B receptor modulators |
| TW202112774A (zh) | 2019-06-14 | 2021-04-01 | 比利時商健生藥品公司 | 經取代之吡唑并-吡啶醯胺及其作為glun2b受體調節劑之用途 |
| JP7667097B2 (ja) | 2019-06-14 | 2025-04-22 | ヤンセン ファーマシューティカ エヌ.ベー. | 置換ピラゾロ-ピリジンアミド及びglun2b受容体調節因子としてのその使用 |
| BR112021025141A2 (pt) | 2019-06-14 | 2022-01-25 | Janssen Pharmaceutica Nv | Pirazolo-piridinas heteroaromáticas substituídas e seu uso como moduladores do receptor glun2b |
| CN114008052A (zh) | 2019-06-14 | 2022-02-01 | 詹森药业有限公司 | 取代的吡唑并-吡嗪以及它们作为GluN2B受体调节剂的用途 |
| WO2023083330A1 (zh) * | 2021-11-12 | 2023-05-19 | 百极优棠(广东)医药科技有限公司 | Drak2抑制剂及其制备方法和应用 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001139561A (ja) | 1999-11-17 | 2001-05-22 | Dainippon Pharmaceut Co Ltd | 5−ハロゲノ−6−(4−トリフルオロメチルフェニル)−4−アミノピリミジン誘導体 |
| JP2008528506A (ja) | 2005-01-19 | 2008-07-31 | ニューロジェン・コーポレーション | ヘテロアリール置換ピペラジニル−ピリジン類縁体 |
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| JP2008528506A (ja) | 2005-01-19 | 2008-07-31 | ニューロジェン・コーポレーション | ヘテロアリール置換ピペラジニル−ピリジン類縁体 |
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| EP3774732A2 (en) | 2021-02-17 |
| US20210340121A1 (en) | 2021-11-04 |
| US20190308950A1 (en) | 2019-10-10 |
| WO2019193516A3 (en) | 2019-12-12 |
| JP2021520381A (ja) | 2021-08-19 |
| WO2019193516A2 (en) | 2019-10-10 |
| EP3774732A4 (en) | 2022-02-09 |
| US11008302B2 (en) | 2021-05-18 |
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