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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| JP7148518B2 (ja) | 2016-12-15 | 2022-10-05 | 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二環式チアジンおよびオキサジン誘導体ならびに使用方法 |
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| JP7148518B2 (ja) | 2016-12-15 | 2022-10-05 | 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二環式チアジンおよびオキサジン誘導体ならびに使用方法 |
| CA3047287A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
| MX387729B (es) | 2016-12-15 | 2025-03-18 | Amgen Inc | Derivados de dióxido de 1,4-tiazina y dióxido 1,2,4-tiadiazina como inhibidores de beta-secretasa y métodos de uso. |
| US10947223B2 (en) | 2016-12-15 | 2021-03-16 | Amgen Inc. | Substituted oxazines as beta-secretase inhibitors |
| WO2018112083A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Thiazine derivatives as beta-secretase inhibitors and methods of use |
-
2017
- 2017-12-13 MX MX2019007104A patent/MX387729B/es unknown
- 2017-12-13 AU AU2017376446A patent/AU2017376446B2/en active Active
- 2017-12-13 CA CA3047290A patent/CA3047290A1/en active Pending
- 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 US US16/466,207 patent/US11021493B2/en active Active
- 2017-12-13 MA MA050007A patent/MA50007A/fr unknown
- 2017-12-13 EP EP17822989.4A patent/EP3555086B1/en active Active
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