JP2020503291A5 - - Google Patents
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- JP2020503291A5 JP2020503291A5 JP2019531721A JP2019531721A JP2020503291A5 JP 2020503291 A5 JP2020503291 A5 JP 2020503291A5 JP 2019531721 A JP2019531721 A JP 2019531721A JP 2019531721 A JP2019531721 A JP 2019531721A JP 2020503291 A5 JP2020503291 A5 JP 2020503291A5
- Authority
- JP
- Japan
- Prior art keywords
- dioxide
- fluoro
- amino
- dihydro
- pyrazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims 119
- -1 cyclopropylethynyl Chemical group 0.000 claims 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 86
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 84
- 229920002554 vinyl polymer Polymers 0.000 claims 82
- 150000003839 salts Chemical class 0.000 claims 57
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 18
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 229910052731 fluorine Inorganic materials 0.000 claims 11
- ILPBINAXDRFYPL-UHFFFAOYSA-N 2-octene Chemical compound CCCCCC=CC ILPBINAXDRFYPL-UHFFFAOYSA-N 0.000 claims 9
- 206010012289 Dementia Diseases 0.000 claims 8
- 229910052799 carbon Inorganic materials 0.000 claims 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- 125000005336 allyloxy group Chemical group 0.000 claims 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 6
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 claims 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 5
- 208000024827 Alzheimer disease Diseases 0.000 claims 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 208000010877 cognitive disease Diseases 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 150000001721 carbon Chemical group 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- SLNHKLHAADKIHP-UHFFFAOYSA-N oct-2-en-3-amine Chemical compound CC=C(CCCCC)N SLNHKLHAADKIHP-UHFFFAOYSA-N 0.000 claims 3
- HFDHAAAQGHEMJE-NKUXOPIZSA-N (1R,4R,5S)-4-[2-fluoro-5-[(Z)-2-fluoro-2-(5-propoxypyrazin-2-yl)ethenyl]phenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCCC)/F)F)S2(=O)=O)CF HFDHAAAQGHEMJE-NKUXOPIZSA-N 0.000 claims 2
- YBTHOLAPRYEQLF-JYTMSLEBSA-N (1R,4R,5S)-4-[5-[(Z)-2-(5-bromopyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(C=C1)Br)F)S2(=O)=O)CF YBTHOLAPRYEQLF-JYTMSLEBSA-N 0.000 claims 2
- TWWUHNNXXQQLLR-LLYJTOGPSA-N (1R,4R,5S)-4-[5-[(Z)-2-(5-ethoxypyrazin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC)F)S2(=O)=O)CF TWWUHNNXXQQLLR-LLYJTOGPSA-N 0.000 claims 2
- QPIIZHRZZDNOGS-JURDMDRRSA-N (1R,4R,5S)-4-[5-[(Z)-2-[5-(2,2-difluoroethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC(F)F)F)S2(=O)=O)CF QPIIZHRZZDNOGS-JURDMDRRSA-N 0.000 claims 2
- GBLGGQWJQJVMRT-XCZGQCRVSA-N (1R,4R,5S)-4-[5-[(Z)-2-[5-(cyclobutylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CCC1)F)S2(=O)=O)CF GBLGGQWJQJVMRT-XCZGQCRVSA-N 0.000 claims 2
- CRXXNYQVRSNKDH-AWTRGSECSA-N (1R,4R,5S)-4-[5-[(Z)-2-[5-(cyclopropylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-1-(fluoromethyl)-4-methyl-8,8-dioxo-8lambda6-thia-3-azabicyclo[3.2.1]oct-2-en-2-amine Chemical compound NC=1[C@]2(CC[C@@H]([C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CC1)F)S2(=O)=O)CF CRXXNYQVRSNKDH-AWTRGSECSA-N 0.000 claims 2
- CXICJNDGGFNJCW-HGDKGACMSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-(5-phenylmethoxypyrazin-2-yl)ethenyl]pyridin-3-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C=1C(=NC=C(C=1)\C=C(/F)\C1=NC=C(N=C1)OCC1=CC=CC=C1)F CXICJNDGGFNJCW-HGDKGACMSA-N 0.000 claims 2
- QDOBYRKWCWCKSV-KEPADWISSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(1,3-oxazol-2-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC=1OC=CN=1)/F)F QDOBYRKWCWCKSV-KEPADWISSA-N 0.000 claims 2
- APCLACYAMMYMOQ-BRAWNXGXSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2,2,2-trifluoroethoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC(F)(F)F)/F)F APCLACYAMMYMOQ-BRAWNXGXSA-N 0.000 claims 2
- NSGTWWITSMDGNM-HVMJPGQCSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC(C(F)F)(F)F)/F)F NSGTWWITSMDGNM-HVMJPGQCSA-N 0.000 claims 2
- ZPZXFRKPLMEIKY-CRCAMNAQSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2-pyrazol-1-ylethoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound N1(N=CC=C1)CCOC=1N=CC(=NC=1)/C(=C/C=1C=CC(=C(C=1)[C@@]1(CS(C(C(=N1)N)(C)C)(=O)=O)C)F)/F ZPZXFRKPLMEIKY-CRCAMNAQSA-N 0.000 claims 2
- VVDGHQXYLSRMAE-PMABOMALSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(3,3,3-trifluoropropoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCCC(F)(F)F)/F)F VVDGHQXYLSRMAE-PMABOMALSA-N 0.000 claims 2
- HRXNXBJPPPFSBG-CPYXBQISSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(trifluoromethyl)pyridin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(C=C1)C(F)(F)F)/F)F HRXNXBJPPPFSBG-CPYXBQISSA-N 0.000 claims 2
- KPJOVXBLKQILFN-YYFKYVOKSA-N (3R)-3-[5-[(Z)-2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(C=C1Cl)C(F)(F)F)F KPJOVXBLKQILFN-YYFKYVOKSA-N 0.000 claims 2
- HNPXSSWNLLKKLT-GFFJUYKFSA-N (3R)-3-[5-[(Z)-2-[5-(cyclobutylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CCC1)F HNPXSSWNLLKKLT-GFFJUYKFSA-N 0.000 claims 2
- IOWBZOMWBOXADA-VLXPNXCBSA-N (3R)-3-[5-[(Z)-2-[5-(cyclohexylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CCCCC1)F IOWBZOMWBOXADA-VLXPNXCBSA-N 0.000 claims 2
- HPOGOBXWTBVPBR-FLYZOPQXSA-N (3R)-3-[5-[(Z)-2-[5-(cyclopentylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CCCC1)F HPOGOBXWTBVPBR-FLYZOPQXSA-N 0.000 claims 2
- WUKZYTGLWVNUQN-UOQNSFNTSA-N (3R)-3-[5-[(Z)-2-[5-(cyclopropylmethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)OCC1CC1)F WUKZYTGLWVNUQN-UOQNSFNTSA-N 0.000 claims 2
- LIGPEDYCRLXVKG-XLPSYMGOSA-N (5R)-5-[2,3-difluoro-5-[(Z)-2-fluoro-2-[5-(1,3-oxazol-2-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C(=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC=1OC=CN=1)/F)F)F)(=O)=O)C LIGPEDYCRLXVKG-XLPSYMGOSA-N 0.000 claims 2
- KCXVXXPLOOYYTO-QWPNKFHKSA-N (5R)-5-[2,3-difluoro-5-[(Z)-2-fluoro-2-[5-(1,3-oxazol-4-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C(=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC=1N=COC=1)/F)F)F)(=O)=O)C KCXVXXPLOOYYTO-QWPNKFHKSA-N 0.000 claims 2
- LITNCVQHGBECBC-QWPNKFHKSA-N (5R)-5-[2,3-difluoro-5-[(Z)-2-fluoro-2-[5-(1,3-thiazol-4-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C(=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC=1N=CSC=1)/F)F)F)(=O)=O)C LITNCVQHGBECBC-QWPNKFHKSA-N 0.000 claims 2
- LLBSPEOFGKBDBA-NSUHCSJYSA-N (5R)-5-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(1,3-oxazol-2-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC=1OC=CN=1)/F)F)(=O)=O)C LLBSPEOFGKBDBA-NSUHCSJYSA-N 0.000 claims 2
- CXUMXNSBNNATPZ-COXIKBTRSA-N (5R)-5-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC(C(F)F)(F)F)/F)F)(=O)=O)C CXUMXNSBNNATPZ-COXIKBTRSA-N 0.000 claims 2
- PMGCFQJAFLPFNY-YLKBSNCHSA-N (5R)-5-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2-methoxypropoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC(C)OC)/F)F)(=O)=O)C PMGCFQJAFLPFNY-YLKBSNCHSA-N 0.000 claims 2
- WBRXXNXHEOFRHH-KVUYCWINSA-N (5R)-5-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(oxetan-3-ylmethoxy)pyrazin-2-yl]ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)OCC1COC1)/F)F)(=O)=O)C WBRXXNXHEOFRHH-KVUYCWINSA-N 0.000 claims 2
- DFZLSFLDVAUKRW-COXIKBTRSA-N (5R)-5-[5-[(Z)-2-([1,3]dioxolo[4,5-c]pyridin-6-yl)-2-fluoroethenyl]-2-fluorophenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound O1COC=2C=NC(=CC=21)/C(=C/C=1C=CC(=C(C=1)[C@]1(N=C(N(S(C1)(=O)=O)C)N)C)F)/F DFZLSFLDVAUKRW-COXIKBTRSA-N 0.000 claims 2
- QCYDNORLXYCIKG-DGJFXRHUSA-N (8R)-8-[2-fluoro-5-[(Z)-2-fluoro-2-(5-prop-2-ynoxypyrazin-2-yl)ethenyl]phenyl]-5,8-dimethyl-4,4-dioxo-4lambda6-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine Chemical compound FC1=C(C=C(C=C1)\C=C(\C1=NC=C(N=C1)OCC#C)/F)[C@]1(N=C(N(S(C11CC1)(=O)=O)C)N)C QCYDNORLXYCIKG-DGJFXRHUSA-N 0.000 claims 2
- XJLBCCOONKOGEU-MPCIYJAUSA-N (8R)-8-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2,2,2-trifluoroethoxy)pyrazin-2-yl]ethenyl]phenyl]-5,8-dimethyl-4,4-dioxo-4lambda6-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine Chemical compound FC1=C(C=C(C=C1)\C=C(\C1=NC=C(N=C1)OCC(F)(F)F)/F)[C@]1(N=C(N(S(C11CC1)(=O)=O)C)N)C XJLBCCOONKOGEU-MPCIYJAUSA-N 0.000 claims 2
- ZCYIFWDSGWZMLK-FBROQIRXSA-N (8R)-8-[2-fluoro-5-[(Z)-2-fluoro-2-[5-[(5-methyl-1,2-oxazol-3-yl)methoxy]pyrazin-2-yl]ethenyl]phenyl]-5,8-dimethyl-4,4-dioxo-4lambda6-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine Chemical compound FC1=C(C=C(C=C1)\C=C(\C1=NC=C(N=C1)OCC1=NOC(=C1)C)/F)[C@]1(N=C(N(S(C11CC1)(=O)=O)C)N)C ZCYIFWDSGWZMLK-FBROQIRXSA-N 0.000 claims 2
- SVTNCINHMKABHR-DVNIYVAHSA-N (8R)-8-[5-[(Z)-2-(5-chloropyrazin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-5,8-dimethyl-4,4-dioxo-4lambda6-thia-5,7-diazaspiro[2.5]oct-6-en-6-amine Chemical compound ClC=1N=CC(=NC=1)/C(=C/C=1C=CC(=C(C=1)[C@]1(N=C(N(S(C11CC1)(=O)=O)C)N)C)F)/F SVTNCINHMKABHR-DVNIYVAHSA-N 0.000 claims 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N 1-nonene Chemical compound CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims 2
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 2
- ZMSIFDIKIXVLDF-UHFFFAOYSA-N 2-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=CO1 ZMSIFDIKIXVLDF-UHFFFAOYSA-N 0.000 claims 2
- FZAXBPZVVJOFKX-UHFFFAOYSA-N 3-methyl-1,2,4-oxadiazole Chemical compound CC=1N=CON=1 FZAXBPZVVJOFKX-UHFFFAOYSA-N 0.000 claims 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims 2
- 208000028698 Cognitive impairment Diseases 0.000 claims 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims 2
- 201000010374 Down Syndrome Diseases 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 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 2
- 206010002022 amyloidosis Diseases 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 230000002490 cerebral effect Effects 0.000 claims 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 2
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| WO2018112084A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
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| CN108997328B (zh) * | 2018-09-06 | 2021-06-08 | 广东东阳光药业有限公司 | 亚氨基噻二嗪二氧化物衍生物及其用途 |
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| JP7149272B2 (ja) | 2016-12-15 | 2022-10-06 | アムジエン・インコーポレーテツド | β－セクレターゼ阻害剤としてのチアジン誘導体および使用方法 |
| EP3555085B1 (en) | 2016-12-15 | 2020-12-02 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
| JP7149271B2 (ja) | 2016-12-15 | 2022-10-06 | アムジエン・インコーポレーテツド | β－セクレターゼ阻害剤としての１，４－チアジンジオキシドおよび１，２，４－チアジアジンジオキシド誘導体ならびに使用方法 |
| WO2018112084A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
| US10947223B2 (en) | 2016-12-15 | 2021-03-16 | Amgen Inc. | Substituted oxazines as beta-secretase inhibitors |
-
2017
- 2017-12-13 JP JP2019531721A patent/JP7149271B2/ja active Active
- 2017-12-13 WO PCT/US2017/066197 patent/WO2018112094A1/en not_active Ceased
- 2017-12-13 CA CA3047290A patent/CA3047290A1/en active Pending
- 2017-12-13 MX MX2019007104A patent/MX387729B/es unknown
- 2017-12-13 AU AU2017376446A patent/AU2017376446B2/en active Active
- 2017-12-13 MA MA050007A patent/MA50007A/fr unknown
- 2017-12-13 US US16/466,207 patent/US11021493B2/en active Active
- 2017-12-13 EP EP17822989.4A patent/EP3555086B1/en active Active
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