JP2020503291A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
Links
- 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
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 230000007505 plaque formation Effects 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- RLCPZPOURNLVTM-WJFAUYEISA-N (1R,4R,5S)-4-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(oxetan-3-ylmethoxy)pyrazin-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)OCC1COC1)/F)F)S2(=O)=O)CF RLCPZPOURNLVTM-WJFAUYEISA-N 0.000 claims 1
- ZWEYAKHRZVCNHF-CPYXBQISSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-(5-fluoropyridin-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)F)/F)F ZWEYAKHRZVCNHF-CPYXBQISSA-N 0.000 claims 1
- ZSGMTRQKPXSNES-SLPYIPCOSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-(5-methoxypyrazin-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)OC)/F)F ZSGMTRQKPXSNES-SLPYIPCOSA-N 0.000 claims 1
- OHCQZOYURJKSAS-NIAMQAJOSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-(5-phenoxypyrazin-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)OC1=CC=CC=C1)/F)F OHCQZOYURJKSAS-NIAMQAJOSA-N 0.000 claims 1
- FHCYHUXVOJOSFM-AYUSBESLSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(2-imidazol-1-ylethoxy)pyrazin-2-yl]ethenyl]phenyl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound N1(C=NC=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 FHCYHUXVOJOSFM-AYUSBESLSA-N 0.000 claims 1
- WSDOPEDHECVJSF-FLYZOPQXSA-N (3R)-3-[2-fluoro-5-[(Z)-2-fluoro-2-[5-(pyridin-4-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)OCC1=CC=NC=C1)/F)F WSDOPEDHECVJSF-FLYZOPQXSA-N 0.000 claims 1
- IEPNSQMIJLNBIV-RSSRPAAFSA-N (3R)-3-[5-[(Z)-2-(5-chloropyrazin-2-yl)-2-fluoroethenyl]-2,3-difluorophenyl]-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)Cl)F)F IEPNSQMIJLNBIV-RSSRPAAFSA-N 0.000 claims 1
- PYRDHKWVKUYQAH-MWNFOORISA-N (3R)-3-[5-[(Z)-2-(5-chloropyrazin-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)Cl)F PYRDHKWVKUYQAH-MWNFOORISA-N 0.000 claims 1
- FJUITDHHAAGQMS-CPYXBQISSA-N (3R)-3-[5-[(Z)-2-(5-chloropyridin-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=C1)Cl)F FJUITDHHAAGQMS-CPYXBQISSA-N 0.000 claims 1
- FCUVGJUTFWKTDD-COXIKBTRSA-N (3S)-3-[5-[(Z)-2-(5-chloropyrazin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-3-(fluoromethyl)-6,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(CF)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)Cl)F FCUVGJUTFWKTDD-COXIKBTRSA-N 0.000 claims 1
- QHUCNZSOEORCHE-WMBZCPDOSA-N (5R)-5-[2-fluoro-5-[(Z)-2-fluoro-2-(5-methoxypyrazin-2-yl)ethenyl]phenyl]-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-3-amine Chemical compound FC1=C(C=C(C=C1)\C=C(\C1=NC=C(N=C1)OC)/F)[C@]1(N=C(N(S(C1)(=O)=O)C)N)C QHUCNZSOEORCHE-WMBZCPDOSA-N 0.000 claims 1
- HEUJXUTVZDSLGX-MEVIEEELSA-N (5R)-5-[5-[(Z)-2-(5-chloropyrazin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-6,6-difluoro-2,2,5-trimethyl-1,1-dioxo-1,4-thiazin-3-amine Chemical compound NC1=N[C@](C(S(C1(C)C)(=O)=O)(F)F)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(N=C1)Cl)F HEUJXUTVZDSLGX-MEVIEEELSA-N 0.000 claims 1
- GVTVQMUQHMNEEL-PSXSOWLISA-N (7R)-7-[5-[(Z)-2-(5-chloropyridin-2-yl)-2-fluoroethenyl]-2-fluorophenyl]-7-methyl-5,5-dioxo-5lambda6-thia-8-azaspiro[3.5]non-8-en-9-amine Chemical compound NC1=N[C@](CS(C11CCC1)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(/F)\C1=NC=C(C=C1)Cl)F GVTVQMUQHMNEEL-PSXSOWLISA-N 0.000 claims 1
- XFVDPSCLJGTGQP-GQNCVOLQSA-N (8R)-8-[2-fluoro-5-[(Z)-2-fluoro-2-[5-[(3-methyl-1,2,4-oxadiazol-5-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=NC(=NO1)C)/F)[C@]1(N=C(N(S(C11CC1)(=O)=O)C)N)C XFVDPSCLJGTGQP-GQNCVOLQSA-N 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- GDVGOJQMSRYKHP-MWNFOORISA-N 5-[(Z)-2-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-1-fluoroethenyl]-1H-pyrazin-2-one Chemical compound NC1=N[C@](CS(C1(C)C)(=O)=O)(C)C1=C(C=CC(=C1)\C=C(\C1=NC=C(N=C1)O)/F)F GDVGOJQMSRYKHP-MWNFOORISA-N 0.000 claims 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 206010048327 Supranuclear palsy Diseases 0.000 claims 1
- 125000003302 alkenyloxy group Chemical group 0.000 claims 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 208000027061 mild cognitive impairment Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000005504 styryl group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662434715P | 2016-12-15 | 2016-12-15 | |
| US62/434,715 | 2016-12-15 | ||
| PCT/US2017/066197 WO2018112094A1 (en) | 2016-12-15 | 2017-12-13 | 1,4-thiazine dioxide and 1,2,4-thiadiazine dioxide derivatives as beta-secretase inhibitors and methods of use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020503291A JP2020503291A (ja) | 2020-01-30 |
| JP2020503291A5 true JP2020503291A5 (enExample) | 2021-01-28 |
| JP7149271B2 JP7149271B2 (ja) | 2022-10-06 |
Family
ID=60888749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019531721A Active JP7149271B2 (ja) | 2016-12-15 | 2017-12-13 | 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 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US11021493B2 (enExample) |
| EP (1) | EP3555086B1 (enExample) |
| JP (1) | JP7149271B2 (enExample) |
| AU (1) | AU2017376446B2 (enExample) |
| CA (1) | CA3047290A1 (enExample) |
| MA (1) | MA50007A (enExample) |
| MX (1) | MX387729B (enExample) |
| WO (1) | WO2018112094A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3555085B1 (en) | 2016-12-15 | 2020-12-02 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
| CA3047286A1 (en) * | 2016-12-15 | 2018-06-21 | Amgen Inc. | Oxazine derivatives as beta-secretase inhibitors and methods of use |
| EP3555106B1 (en) | 2016-12-15 | 2022-03-09 | Amgen Inc. | Bicyclic thiazine and oxazine 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. |
| 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 |
| CN109180672A (zh) * | 2018-09-29 | 2019-01-11 | 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 |
| CN110078613B (zh) * | 2019-05-31 | 2022-04-22 | 杭州科耀医药科技有限公司 | 一种2-卤-5-碘苯甲酸的合成方法 |
| WO2021175669A1 (en) | 2020-03-04 | 2021-09-10 | Basf Se | Use of substituted 1,2,4-oxadiazoles for combating phytopathogenic fungi |
| WO2022074631A1 (en) * | 2020-10-11 | 2022-04-14 | Dynarx Technology (India) Ltd | A process for preparing sglt2 inhibitor intermediate 2-chloro-5-iodobenzoic acid |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5441870A (en) | 1992-04-15 | 1995-08-15 | Athena Neurosciences, Inc. | Methods for monitoring cellular processing of β-amyloid precursor protein |
| SI9300303A (en) | 1993-06-08 | 1994-12-31 | Krka Tovarna Zdravil | Process for isolation of hypolipemic effective substance |
| JPH11507538A (ja) | 1995-06-07 | 1999-07-06 | アテナ ニューロサイエンシズ インコーポレイティド | β−セクレターゼ、β−セクレターゼに対する抗体、及びβ−セクレターゼ阻害を検出するためのアッセイ |
| KR100768381B1 (ko) | 1998-09-24 | 2007-10-18 | 파마시아 앤드 업존 캄파니 엘엘씨 | 알츠하이머병 세크레타제 |
| ES2476027T3 (es) | 2005-10-25 | 2014-07-11 | Shionogi & Co., Ltd. | Derivados de aminodihidrotriazina |
| WO2008133273A1 (ja) | 2007-04-24 | 2008-11-06 | Shionogi & Co., Ltd. | アルツハイマー症治療用医薬組成物 |
| KR20100017255A (ko) | 2007-04-24 | 2010-02-16 | 시오노기 앤드 컴파니, 리미티드 | 환식기로 치환된 아미노다이하이드로싸이아진 유도체 |
| HRP20151030T1 (hr) | 2008-01-18 | 2015-11-06 | Eisai R&D Management Co., Ltd. | Kondenzirani derivat aminodihidrotiazina |
| TWI431004B (zh) | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
| MX2010013256A (es) | 2008-06-13 | 2010-12-21 | Shionogi & Co | Derivado heterociclico que contiene azufre que tiene actividad inhibitoria de beta-secretasa. |
| AU2009277485B2 (en) | 2008-07-28 | 2013-05-02 | Eisai R&D Management Co., Ltd. | Spiroaminodihydrothiazine derivatives |
| WO2010013302A1 (ja) | 2008-07-28 | 2010-02-04 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スピロアミノジヒドロチアジン誘導体 |
| WO2010038686A1 (ja) | 2008-09-30 | 2010-04-08 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 新規な縮合アミノジヒドロチアジン誘導体 |
| AR077277A1 (es) | 2009-07-09 | 2011-08-17 | Lilly Co Eli | Compuestos de biciclo (1,3)tiazin-2-amina formulacion farmaceutica que lo comprende y su uso para la manufactura de un medicamento util para el tratamiento de la enfermedad de alzheimer |
| GB0912778D0 (en) | 2009-07-22 | 2009-08-26 | Eisai London Res Lab Ltd | Fused aminodihydro-oxazine derivatives |
| US20110065695A1 (en) | 2009-09-11 | 2011-03-17 | Jeremy Beauchamp | Use of aminodihydrothiazines for the treatment or prevention of diabetes |
| US9308660B2 (en) | 2009-10-06 | 2016-04-12 | Emerson Electric Co. | Plastic pipe cutter |
| UA108363C2 (uk) * | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| EP2500344A4 (en) | 2009-11-13 | 2013-05-01 | Shionogi & Co | AMINOTHIAZIN OR AMINOOXAZINE DERIVATIVES WITH AN AMINO TERMINATION |
| JPWO2011070781A1 (ja) | 2009-12-09 | 2013-04-22 | 塩野義製薬株式会社 | 置換アミノチアジン誘導体 |
| UA103272C2 (uk) | 2009-12-11 | 2013-09-25 | Ф. Хоффманн-Ля Рош Аг | 2-аміно-5,5-дифтор-5,6-дигідро-4h-оксазини як інгібітори bace1 і/або bace2 |
| JPWO2011071135A1 (ja) | 2009-12-11 | 2013-04-22 | 塩野義製薬株式会社 | オキサジン誘導体 |
| CA2824097A1 (en) | 2011-01-12 | 2012-07-19 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
| MA34898B1 (fr) | 2011-01-13 | 2014-02-01 | Novartis Ag | Nouveaux dérivés hétérocycliques et leur utilisation dans le traitement de troubles neurologiques |
| GB201101139D0 (en) | 2011-01-21 | 2011-03-09 | Eisai Ltd | Fused aminodihydrothiazine derivatives |
| GB201101140D0 (en) | 2011-01-21 | 2011-03-09 | Eisai Ltd | Fused aminodihydrothiazine derivatives |
| EP2694489B1 (en) * | 2011-04-07 | 2017-09-06 | Merck Sharp & Dohme Corp. | C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2694521B1 (en) | 2011-04-07 | 2015-11-25 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| WO2012139425A1 (en) * | 2011-04-13 | 2012-10-18 | Schering Corporation | 5-substituted iminothiazines and their mono-and dioxides as bace inhibitors,compositions,and their use |
| CN103649082A (zh) | 2011-04-26 | 2014-03-19 | 盐野义制药株式会社 | 吡啶衍生物和含有该吡啶衍生物的bace1抑制剂 |
| EP2517898A1 (de) | 2011-04-29 | 2012-10-31 | Lanxess Deutschland GmbH | Kieselsäurehaltige Kautschukmischungen mit schwefelhaltigen Additiven |
| US8785436B2 (en) | 2011-05-16 | 2014-07-22 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE 1 and/or BACE2 inhibitors |
| US8598161B2 (en) | 2011-05-24 | 2013-12-03 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| US8604024B2 (en) | 2011-05-24 | 2013-12-10 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| US8927535B2 (en) | 2011-07-06 | 2015-01-06 | Hoffman-La Roche Inc. | Cyclopropyl-fused-1,3-thiazepines as BACE1 and/or BACE2 inhibitors |
| BR112014004181A2 (pt) | 2011-08-22 | 2017-06-13 | Merck Sharp & Dohme | composto, composição farmacêutica, e, método de tratamento, prevenção, e / ou retardo do início de uma doença ou patologia |
| UY34278A (es) | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
| WO2013030713A1 (en) | 2011-08-31 | 2013-03-07 | Pfizer Inc. | Hexahydropyrano [3,4-d][1,3] thiazin-2-amine compounds |
| WO2013142613A1 (en) | 2012-03-20 | 2013-09-26 | Elan Pharmaceuticals, Inc. | Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof |
| WO2013164730A1 (en) | 2012-05-04 | 2013-11-07 | Pfizer Inc. | Heterocyclic substituted hexahydropyrano [3,4-d] [1,3] thiazin- 2 -amine compounds as inhibitors of app, bace1 and bace 2. |
| WO2013182638A1 (en) | 2012-06-08 | 2013-12-12 | H. Lundbeck A/S | 2 -aminothiazinylheteroaryls as bace1 inhibitors for the treatment alzheimer's disease |
| GB201212871D0 (en) | 2012-07-20 | 2012-09-05 | Eisai Ltd | Novel compounds |
| JP2015529239A (ja) | 2012-09-20 | 2015-10-05 | ファイザー・インク | アルキル置換ヘキサヒドロピラノ［３，４−ｄ］［１，３］チアジン−２−アミン化合物 |
| WO2014059185A1 (en) | 2012-10-12 | 2014-04-17 | Amgen Inc. | Amino - dihydrothiazine and amino - dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use |
| EP2908825B1 (en) | 2012-10-17 | 2018-04-18 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| WO2014062553A1 (en) | 2012-10-17 | 2014-04-24 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2912035A4 (en) | 2012-10-24 | 2016-06-15 | Shionogi & Co | DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY |
| US9328124B2 (en) | 2012-10-26 | 2016-05-03 | Eli Lilly And Company | BACE inhibitors |
| 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 |
| WO2014098831A1 (en) | 2012-12-19 | 2014-06-26 | Bristol-Myers Squibb Company | 4,6-diarylaminothiazines as bace1 inhibitors and their use for the reduction of beta-amyloid production |
| CA2893333C (en) | 2012-12-19 | 2017-10-24 | Pfizer Inc. | Carbocyclic-and heterocyclic-substituted hexahydropyrano[3,4-d][1,3]thiazin-2-amine compounds |
| CN104870000A (zh) | 2012-12-20 | 2015-08-26 | 默沙东公司 | 作为bace抑制剂的c5,c6氧杂环稠合的亚胺基噻嗪二氧化物化合物,组合物及其用途 |
| EP2934534B1 (en) | 2012-12-21 | 2017-12-13 | Merck Sharp & Dohme Corp. | C5-spiro iminothiadiazine dioxides as bace inhibitors |
| JP6374889B2 (ja) | 2013-03-08 | 2018-08-15 | 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過フッ素化シクロプロピル縮合１，３−オキサジン−２−アミン化合物、及び使用方法 |
| TWI593692B (zh) | 2013-03-12 | 2017-08-01 | 美國禮來大藥廠 | 四氫吡咯并噻嗪化合物 |
| US9550762B2 (en) | 2014-08-08 | 2017-01-24 | Amgen, Inc. | Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| SG11201708027XA (en) | 2015-04-21 | 2017-11-29 | Allgenesis Biotherapeutics Inc | Compounds and their use as bace1 inhibitors |
| WO2017024180A1 (en) | 2015-08-06 | 2017-02-09 | Amgen Inc. | Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| EP3555106B1 (en) | 2016-12-15 | 2022-03-09 | Amgen Inc. | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
| CA3047286A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Oxazine derivatives as beta-secretase inhibitors and methods of use |
| EP3555084B1 (en) | 2016-12-15 | 2022-03-16 | Amgen Inc. | 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. |
| EP3555085B1 (en) | 2016-12-15 | 2020-12-02 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
-
2017
- 2017-12-13 MX MX2019007104A patent/MX387729B/es unknown
- 2017-12-13 US US16/466,207 patent/US11021493B2/en active Active
- 2017-12-13 EP EP17822989.4A patent/EP3555086B1/en active Active
- 2017-12-13 MA MA050007A patent/MA50007A/fr unknown
- 2017-12-13 WO PCT/US2017/066197 patent/WO2018112094A1/en not_active Ceased
- 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
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2020503291A5 (enExample) | ||
| JP7126541B2 (ja) | ハンチントンタンパク質のイメージング用プローブ | |
| JP5911638B2 (ja) | ベンゾチアゾール−６−イル酢酸誘導体およびｈｉｖ感染を処置するためのそれらの使用 | |
| IL320682A (en) | Protein tyrosine phosphatase inhibitors | |
| JP2020514267A5 (enExample) | ||
| KR20190080897A (ko) | 치환된 피리디논 함유 트리시클릭 화합물, 및 그의 사용 방법 | |
| CN106414429B (zh) | 吡唑化合物及其作为t型钙通道阻断剂的用途 | |
| US20150291598A1 (en) | Compounds and compositions for the treatment of parasitic diseases | |
| TW201831464A (zh) | 作為激酶抑制劑之雜環醯胺 | |
| JP2017531039A5 (enExample) | ||
| RU2012105284A (ru) | Спиро-аминосоединения, пригодные для лечения нарушений сна и лекарственного привыкания | |
| TWI803600B (zh) | 新穎的三唑酮衍生物或其鹽及包含彼等之醫藥組合物 | |
| JP2020503294A5 (enExample) | ||
| JP2016511258A5 (enExample) | ||
| JP2017523223A5 (enExample) | ||
| JP2020503293A5 (enExample) | ||
| JP2018508553A5 (enExample) | ||
| US9890171B2 (en) | Aldosterone synthase inhibitors | |
| JP2018512062A5 (enExample) | ||
| JP2019537581A5 (enExample) | ||
| AU2015212495A1 (en) | Antibacterial combinations comprising polymyxin | |
| JP2024530208A (ja) | カリウムチャネルモジュレーター | |
| JP2011520951A (ja) | 抗マラリア薬としての新規なテトラヒドロイソキノリン類 | |
| JP2021187859A (ja) | 複素環化合物の医薬用途 | |
| TWI903404B (zh) | 雜環化合物 |