JP2016511258A5 - - Google Patents
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- Publication number
- JP2016511258A5 JP2016511258A5 JP2015560325A JP2015560325A JP2016511258A5 JP 2016511258 A5 JP2016511258 A5 JP 2016511258A5 JP 2015560325 A JP2015560325 A JP 2015560325A JP 2015560325 A JP2015560325 A JP 2015560325A JP 2016511258 A5 JP2016511258 A5 JP 2016511258A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- amino
- independently
- oxazin
- dihydro
- 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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- -1 CH 2 OH Chemical group 0.000 claims 109
- 125000000217 alkyl group Chemical group 0.000 claims 59
- 150000001875 compounds Chemical class 0.000 claims 42
- 229910052731 fluorine Inorganic materials 0.000 claims 37
- 229910052799 carbon Inorganic materials 0.000 claims 32
- 150000003839 salts Chemical class 0.000 claims 31
- 229910052739 hydrogen Inorganic materials 0.000 claims 30
- 125000003342 alkenyl group Chemical group 0.000 claims 29
- 125000004432 carbon atom Chemical group C* 0.000 claims 28
- 229910052757 nitrogen Inorganic materials 0.000 claims 28
- 125000000304 alkynyl group Chemical group 0.000 claims 27
- 125000005842 heteroatom Chemical group 0.000 claims 27
- 229910052760 oxygen Inorganic materials 0.000 claims 24
- 229910052801 chlorine Inorganic materials 0.000 claims 23
- 125000005309 thioalkoxy group Chemical group 0.000 claims 21
- 125000001153 fluoro group Chemical group F* 0.000 claims 20
- 125000001424 substituent group Chemical group 0.000 claims 20
- 125000004663 dialkyl amino group Chemical group 0.000 claims 19
- 125000003545 alkoxy group Chemical group 0.000 claims 14
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims 14
- 125000002757 morpholinyl group Chemical group 0.000 claims 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 13
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 12
- 125000003282 alkyl amino group Chemical group 0.000 claims 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 12
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 11
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 11
- 125000000842 isoxazolyl group Chemical group 0.000 claims 11
- 125000001188 haloalkyl group Chemical group 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 9
- 239000008194 pharmaceutical composition Substances 0.000 claims 9
- 229910052717 sulfur Inorganic materials 0.000 claims 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 8
- QMYGFTJCQFEDST-UHFFFAOYSA-N 3-methoxybutyl acetate Chemical group COC(C)CCOC(C)=O QMYGFTJCQFEDST-UHFFFAOYSA-N 0.000 claims 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 7
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 7
- 239000012453 solvate Substances 0.000 claims 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims 5
- 206010012289 Dementia Diseases 0.000 claims 4
- 125000002619 bicyclic group Chemical group 0.000 claims 4
- 125000002950 monocyclic group Chemical group 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 229940125810 compound 20 Drugs 0.000 claims 2
- 229940126086 compound 21 Drugs 0.000 claims 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- IDHAZTOESFWNSY-WMLDXEAASA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C1F IDHAZTOESFWNSY-WMLDXEAASA-N 0.000 claims 2
- LUIXXFPAAMIKOX-LRDDRELGSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-5-chloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=CC=2)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 LUIXXFPAAMIKOX-LRDDRELGSA-N 0.000 claims 2
- GZQHKBFOERBNAG-GUYCJALGSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-5-cyanopyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(=CC=2)C#N)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 GZQHKBFOERBNAG-GUYCJALGSA-N 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- PCNDBEIQPLJGIC-KUHUBIRLSA-N (4r,6r)-4-[2-fluoro-5-[(2-methoxypyrido[3,4-b]pyrazin-5-yl)amino]phenyl]-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-2-amine Chemical compound N=1C=CC2=NC(OC)=CN=C2C=1NC(C=1)=CC=C(F)C=1[C@@]1(CF)C[C@H](C(F)(F)F)OC(N)=N1 PCNDBEIQPLJGIC-KUHUBIRLSA-N 0.000 claims 1
- CCHOGVQCNCTVED-HNAYVOBHSA-N (4s,6s)-4-[5-[(3-chloro-1,7-naphthyridin-8-yl)amino]-2-fluorophenyl]-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-2-amine Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC=2C3=NC=C(Cl)C=C3C=CN=2)=CC=C1F CCHOGVQCNCTVED-HNAYVOBHSA-N 0.000 claims 1
- GDGGLXWHVCHUOD-SJCJKPOMSA-N (4s,6s)-4-[5-[(7-chloropyrido[3,2-d]pyrimidin-4-yl)amino]-2-fluoropyridin-3-yl]-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-2-amine Chemical compound C=1C(NC=2C3=NC=C(Cl)C=C3N=CN=2)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 GDGGLXWHVCHUOD-SJCJKPOMSA-N 0.000 claims 1
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims 1
- KJBKHJJJGKNGTR-UGSOOPFHSA-N 4-[[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]amino]pyrido[3,2-d]pyrimidine-7-carbonitrile Chemical compound C=1C(NC=2C3=NC=C(C=C3N=CN=2)C#N)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 KJBKHJJJGKNGTR-UGSOOPFHSA-N 0.000 claims 1
- QJQLEDGUNULCGG-OXJNMPFZSA-N 8-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluoroanilino]-1,7-naphthyridine-3-carbonitrile Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC=2C3=NC=C(C=C3C=CN=2)C#N)=CC=C1F QJQLEDGUNULCGG-OXJNMPFZSA-N 0.000 claims 1
- LWXHQLQQXIEDPY-OXJNMPFZSA-N 8-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluoroanilino]-5-fluoro-1,7-naphthyridine-3-carbonitrile Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC=2C3=NC=C(C=C3C(F)=CN=2)C#N)=CC=C1F LWXHQLQQXIEDPY-OXJNMPFZSA-N 0.000 claims 1
- VFSFJNSLXGLHOI-LIRRHRJNSA-N 8-[[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]amino]-1,7-naphthyridine-3-carbonitrile Chemical compound C=1C(NC=2C3=NC=C(C=C3C=CN=2)C#N)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 VFSFJNSLXGLHOI-LIRRHRJNSA-N 0.000 claims 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims 1
- 206010002022 amyloidosis Diseases 0.000 claims 1
- 210000004227 basal ganglia Anatomy 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 230000003412 degenerative effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 210000004558 lewy body Anatomy 0.000 claims 1
- 208000027061 mild cognitive impairment Diseases 0.000 claims 1
- BLNHQDSKCVQIOQ-GUYCJALGSA-N n-[3-[(4r,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound C1=NC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 BLNHQDSKCVQIOQ-GUYCJALGSA-N 0.000 claims 1
- SXGOGHFRCNZQNM-SUMWQHHRSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-3,5-dichloropyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C1F SXGOGHFRCNZQNM-SUMWQHHRSA-N 0.000 claims 1
- MOMLEQNWBDCETG-KBXCAEBGSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C1F MOMLEQNWBDCETG-KBXCAEBGSA-N 0.000 claims 1
- DDSHXFILKTVOHT-KBXCAEBGSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-3-chloro-5-methoxypyridine-2-carboxamide Chemical compound ClC1=CC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 DDSHXFILKTVOHT-KBXCAEBGSA-N 0.000 claims 1
- VBRNPACCSYLXRZ-MGPUTAFESA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-3-methylimidazo[1,2-a]pyridine-2-carboxamide Chemical compound N1=C2C=CC=CN2C(C)=C1C(=O)NC(C=1)=CC=C(F)C=1[C@]1(CF)C[C@@H](C(F)(F)F)OC(N)=N1 VBRNPACCSYLXRZ-MGPUTAFESA-N 0.000 claims 1
- GXYRXKLMYVNONT-MAUKXSAKSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2N=CC(OCC(F)(F)F)=CC=2)=CC=C1F GXYRXKLMYVNONT-MAUKXSAKSA-N 0.000 claims 1
- BWKHCKWUYYLDFL-SUMWQHHRSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-bromo-3-chloropyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2C(=CC(Br)=CN=2)Cl)=CC=C1F BWKHCKWUYYLDFL-SUMWQHHRSA-N 0.000 claims 1
- QKABRHMRLFQOCY-WMLDXEAASA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F QKABRHMRLFQOCY-WMLDXEAASA-N 0.000 claims 1
- OJXHVKRDKPVNQU-KBXCAEBGSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloro-3-methoxypyridine-2-carboxamide Chemical compound COC1=CC(Cl)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 OJXHVKRDKPVNQU-KBXCAEBGSA-N 0.000 claims 1
- GSHVOYWQLKOCLX-KBXCAEBGSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloro-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(Cl)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 GSHVOYWQLKOCLX-KBXCAEBGSA-N 0.000 claims 1
- CBFVEIDAVVTRFQ-HNAYVOBHSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 CBFVEIDAVVTRFQ-HNAYVOBHSA-N 0.000 claims 1
- QCMXWFUAVCHHIA-MAUKXSAKSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2N=CC(=CC=2)C#N)=CC=C1F QCMXWFUAVCHHIA-MAUKXSAKSA-N 0.000 claims 1
- NJIHNSPWTBSFKB-WMLDXEAASA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide Chemical compound C1[C@@H](C(F)(F)F)OC(N)=N[C@]1(CF)C1=CC(NC(=O)C=2N=CC(F)=CC=2)=CC=C1F NJIHNSPWTBSFKB-WMLDXEAASA-N 0.000 claims 1
- FOWQPYBFNSIGLL-SCLBCKFNSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-methoxy-3-methylpyrazine-2-carboxamide Chemical compound CC1=NC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 FOWQPYBFNSIGLL-SCLBCKFNSA-N 0.000 claims 1
- BLNHQDSKCVQIOQ-SUMWQHHRSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound C1=NC(OC)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 BLNHQDSKCVQIOQ-SUMWQHHRSA-N 0.000 claims 1
- HHBMLXDPSJOPLK-MAUKXSAKSA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-methoxypyridine-2-carboxamide Chemical compound N1=CC(OC)=CC=C1C(=O)NC1=CC=C(F)C([C@@]2(CF)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 HHBMLXDPSJOPLK-MAUKXSAKSA-N 0.000 claims 1
- HCDBRYXKOZVMHM-MGPUTAFESA-N n-[3-[(4s,6s)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-6-chloro-3-methylimidazo[1,2-a]pyridine-2-carboxamide Chemical compound N1=C2C=CC(Cl)=CN2C(C)=C1C(=O)NC(C=1)=CC=C(F)C=1[C@]1(CF)C[C@@H](C(F)(F)F)OC(N)=N1 HCDBRYXKOZVMHM-MGPUTAFESA-N 0.000 claims 1
- FLOQLFHUIOTUTO-KSSFIOAISA-N n-[3-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloro-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(Cl)=CN=C1C(=O)NC1=CC=C(F)C([C@@]2(C)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 FLOQLFHUIOTUTO-KSSFIOAISA-N 0.000 claims 1
- GLPZXCBSTJTISQ-YOEHRIQHSA-N n-[3-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 GLPZXCBSTJTISQ-YOEHRIQHSA-N 0.000 claims 1
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- WTQJLKGKDKGXBB-ZBEGNZNMSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-3,5-dichloropyridine-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CN=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 WTQJLKGKDKGXBB-ZBEGNZNMSA-N 0.000 claims 1
- QDBLNVMBHVAXAF-SJCJKPOMSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-3-chloro-5-methoxypyridine-2-carboxamide Chemical compound ClC1=CC(OC)=CN=C1C(=O)NC1=CN=C(F)C([C@@]2(C)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 QDBLNVMBHVAXAF-SJCJKPOMSA-N 0.000 claims 1
- OYOWKRLQEBXXFF-SJCJKPOMSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-5-chloro-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(Cl)=CN=C1C(=O)NC1=CN=C(F)C([C@@]2(C)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 OYOWKRLQEBXXFF-SJCJKPOMSA-N 0.000 claims 1
- AOLLQRLVRFPHMU-UGSOOPFHSA-N n-[5-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-6-fluoropyridin-3-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(C#N)=CN=C1C(=O)NC1=CN=C(F)C([C@@]2(C)N=C(N)O[C@@H](C2)C(F)(F)F)=C1 AOLLQRLVRFPHMU-UGSOOPFHSA-N 0.000 claims 1
- RPUXRRILZNMEFF-QFYYESIMSA-N n-[6-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-5-fluoropyridin-2-yl]-3,5-dichloropyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 RPUXRRILZNMEFF-QFYYESIMSA-N 0.000 claims 1
- XUSLPMBGYMTYIP-QFYYESIMSA-N n-[6-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-5-fluoropyridin-2-yl]-3-chloro-5-(trifluoromethyl)pyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C(F)(F)F)Cl)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 XUSLPMBGYMTYIP-QFYYESIMSA-N 0.000 claims 1
- SEDNJKRDPITJTN-GTNSWQLSSA-N n-[6-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-5-fluoropyridin-2-yl]-3-chloro-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2C(=CC(=CN=2)C#N)Cl)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 SEDNJKRDPITJTN-GTNSWQLSSA-N 0.000 claims 1
- FWHRMLYVMNQBGS-ZBEGNZNMSA-N n-[6-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-5-fluoropyridin-2-yl]-5-chloropyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 FWHRMLYVMNQBGS-ZBEGNZNMSA-N 0.000 claims 1
- JDFWETJUGPKDKZ-SJCJKPOMSA-N n-[6-[(4s,6s)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-1,3-oxazin-4-yl]-5-fluoropyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound N=1C(NC(=O)C=2N=CC(=CC=2)C#N)=CC=C(F)C=1[C@]1(C)C[C@@H](C(F)(F)F)OC(N)=N1 JDFWETJUGPKDKZ-SJCJKPOMSA-N 0.000 claims 1
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| WO2014134341A1 (en) | 2013-03-01 | 2014-09-04 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| AP2015008716A0 (en) | 2013-03-08 | 2015-09-30 | Amgen Inc | Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| AU2014253275B2 (en) | 2013-04-11 | 2018-10-18 | F. Hoffmann-La Roche Ag | BACE1 inhibitors |
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| LT2912041T (lt) | 2012-10-26 | 2017-03-10 | Eli Lilly And Company | Tetrahidropiroltiazino dariniai kaip bace slopikliai |
| US9447085B2 (en) | 2012-12-14 | 2016-09-20 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxides containing a thioamide, amidine, or amide oxime group as BACE inhibitors, compositions, and their use |
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| EP2934534B1 (en) | 2012-12-21 | 2017-12-13 | Merck Sharp & Dohme Corp. | C5-spiro iminothiadiazine dioxides as bace inhibitors |
| BR112015016315A2 (pt) * | 2013-01-22 | 2017-07-11 | Hoffmann La Roche | fluoro-[1,3]oxazinas como inibidores de bace1 |
| WO2014134341A1 (en) | 2013-03-01 | 2014-09-04 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| AP2015008716A0 (en) | 2013-03-08 | 2015-09-30 | Amgen Inc | Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| AU2014253275B2 (en) * | 2013-04-11 | 2018-10-18 | F. Hoffmann-La Roche Ag | BACE1 inhibitors |
| SG11201508814SA (en) | 2013-04-26 | 2015-11-27 | Hoffmann La Roche | Synthesis of bace inhibitors |
-
2014
- 2014-02-27 WO PCT/US2014/019100 patent/WO2014134341A1/en not_active Ceased
- 2014-02-27 CA CA2902212A patent/CA2902212C/en active Active
- 2014-02-27 AU AU2014223334A patent/AU2014223334C1/en active Active
- 2014-02-27 EP EP14712418.4A patent/EP2961749B1/en active Active
- 2014-02-27 US US14/192,710 patent/US9296734B2/en active Active
- 2014-02-27 TW TW103106910A patent/TW201446758A/zh unknown
- 2014-02-27 MX MX2015011313A patent/MX366855B/es active IP Right Grant
- 2014-02-27 JP JP2015560325A patent/JP6389830B2/ja active Active
- 2014-03-05 UY UY0001035361A patent/UY35361A/es not_active Application Discontinuation
-
2018
- 2018-06-25 AU AU2018204589A patent/AU2018204589A1/en not_active Abandoned
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