JP2018513191A5 - - Google Patents
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- JP2018513191A5 JP2018513191A5 JP2017555545A JP2017555545A JP2018513191A5 JP 2018513191 A5 JP2018513191 A5 JP 2018513191A5 JP 2017555545 A JP2017555545 A JP 2017555545A JP 2017555545 A JP2017555545 A JP 2017555545A JP 2018513191 A5 JP2018513191 A5 JP 2018513191A5
- Authority
- JP
- Japan
- Prior art keywords
- imino
- hydrogen
- alkyl
- deuterium
- halogen
- 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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- 125000000217 alkyl group Chemical group 0.000 claims 169
- 229910052739 hydrogen Inorganic materials 0.000 claims 126
- 239000001257 hydrogen Substances 0.000 claims 126
- 150000002431 hydrogen Chemical class 0.000 claims 124
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 97
- 229910052805 deuterium Inorganic materials 0.000 claims 97
- 229910052736 halogen Inorganic materials 0.000 claims 97
- 150000002367 halogens Chemical class 0.000 claims 97
- 125000001188 haloalkyl group Chemical group 0.000 claims 72
- 125000000753 cycloalkyl group Chemical group 0.000 claims 57
- 125000004404 heteroalkyl group Chemical group 0.000 claims 54
- -1 2- (2-methylpent-3-yn-2-yl)-1H-benzo [d] imidazol-6-yl Chemical group 0.000 claims 53
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 50
- 125000001072 heteroaryl group Chemical group 0.000 claims 44
- 125000000304 alkynyl group Chemical group 0.000 claims 37
- 150000001875 compounds Chemical class 0.000 claims 36
- 239000000651 prodrug Chemical group 0.000 claims 36
- 229940002612 prodrug Drugs 0.000 claims 36
- 125000003118 aryl group Chemical group 0.000 claims 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 34
- 125000003342 alkenyl group Chemical group 0.000 claims 30
- 150000003839 salts Chemical class 0.000 claims 28
- 239000012453 solvate Substances 0.000 claims 26
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 24
- 229910052757 nitrogen Inorganic materials 0.000 claims 24
- 229910052717 sulfur Inorganic materials 0.000 claims 22
- 229910052799 carbon Inorganic materials 0.000 claims 19
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims 18
- 150000001721 carbon Chemical class 0.000 claims 17
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 14
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 14
- 125000003545 alkoxy group Chemical group 0.000 claims 14
- 125000003368 amide group Chemical group 0.000 claims 14
- 125000003277 amino group Chemical group 0.000 claims 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 13
- 239000012458 free base Substances 0.000 claims 12
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims 11
- 125000004432 carbon atom Chemical group C* 0.000 claims 11
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 9
- 125000005018 aryl alkenyl group Chemical group 0.000 claims 9
- 125000005015 aryl alkynyl group Chemical group 0.000 claims 9
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims 9
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 7
- 208000024827 Alzheimer disease Diseases 0.000 claims 5
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 4
- UQDUPQYQJKYHQI-UHFFFAOYSA-N dodecanoic acid methyl ester Natural products CCCCCCCCCCCC(=O)OC UQDUPQYQJKYHQI-UHFFFAOYSA-N 0.000 claims 4
- HSEMFIZWXHQJAE-UHFFFAOYSA-N hexadecanamide Chemical compound CCCCCCCCCCCCCCCC(N)=O HSEMFIZWXHQJAE-UHFFFAOYSA-N 0.000 claims 4
- 229940095102 methyl benzoate Drugs 0.000 claims 4
- HABIAKDIZVCTLU-UHFFFAOYSA-N 1,3-diazinan-4-one Chemical compound O=C1CCNCN1 HABIAKDIZVCTLU-UHFFFAOYSA-N 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 3
- 125000003367 polycyclic group Chemical group 0.000 claims 3
- TYFDPTNOAQWDOO-QFIPXVFZSA-N (3R)-3,6,6-trimethyl-1,1-dioxo-3-(8-prop-1-ynyldibenzothiophen-2-yl)-2H-1,4-thiazin-5-amine Chemical compound NC1=N[C@@](CS(C1(C)C)(=O)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C TYFDPTNOAQWDOO-QFIPXVFZSA-N 0.000 claims 2
- KYWPORDLBGCZCA-NRFANRHFSA-N (3R)-3,6,6-trimethyl-3-(2-methyl-6,11-dihydro-5H-pyrido[2,3-b][1]benzazepin-9-yl)-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound N=C1N[C@@](CS(C1(C)C)(=O)=O)(C=1C=CC2=C(NC3=C(CC2)C=CC(=N3)C)C=1)C KYWPORDLBGCZCA-NRFANRHFSA-N 0.000 claims 2
- KGKREPAGYWRXPP-QFIPXVFZSA-N (3R)-3-(3-fluoro-8-prop-1-ynyldibenzothiophen-2-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)C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1F KGKREPAGYWRXPP-QFIPXVFZSA-N 0.000 claims 2
- GKXUSAOGOMMRHV-QFIPXVFZSA-N (3R)-3-(7-fluoro-8-prop-1-ynyldibenzothiophen-2-yl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound FC1=CC2=C(C3=C(S2)C=CC(=C3)[C@@]2(CS(C(C(N2)=N)(C)C)(=O)=O)C)C=C1C#CC GKXUSAOGOMMRHV-QFIPXVFZSA-N 0.000 claims 2
- KWRKQLLZTAYYTI-NRFANRHFSA-N (3R)-5-amino-1,3-dimethyl-3-(8-prop-1-ynyldibenzothiophen-2-yl)-2H-pyrazin-6-one Chemical compound CC#Cc1ccc2sc3ccc(cc3c2c1)[C@]1(C)CN(C)C(=O)C(N)=N1 KWRKQLLZTAYYTI-NRFANRHFSA-N 0.000 claims 2
- IHSBXFYIRGZLBH-FQEVSTJZSA-N (5R)-2,5-dimethyl-1,1-dioxo-5-(8-prop-1-ynyldibenzothiophen-2-yl)-6H-1,2,4-thiadiazin-3-amine Chemical compound CC#Cc1ccc2sc3ccc(cc3c2c1)[C@]1(C)CS(=O)(=O)N(C)C(N)=N1 IHSBXFYIRGZLBH-FQEVSTJZSA-N 0.000 claims 2
- UISDNDOYIIVJRO-NRFANRHFSA-N (6R)-6-methyl-4,4-dioxo-6-(8-prop-1-ynyldibenzothiophen-2-yl)-4lambda6-thia-7-azaspiro[2.5]oct-7-en-8-amine Chemical compound N=C1N[C@@](CS(C11CC1)(=O)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C UISDNDOYIIVJRO-NRFANRHFSA-N 0.000 claims 2
- CHVZRQQWCYNRLR-NDEPHWFRSA-N (6S)-1-benzoyl-2-imino-3,6-dimethyl-6-(8-prop-1-ynyldibenzothiophen-2-yl)-1,3-diazinan-4-one Chemical compound CC#Cc1ccc2sc3ccc(cc3c2c1)[C@]1(C)CC(=O)N(C)C(=N)N1C(=O)c1ccccc1 CHVZRQQWCYNRLR-NDEPHWFRSA-N 0.000 claims 2
- MTFXAMCNSZAEJY-QNGWXLTQSA-N (6S)-1-hexadecanoyl-2-imino-3,6-dimethyl-6-(8-prop-1-ynyldibenzothiophen-2-yl)-1,3-diazinan-4-one Chemical compound CCCCCCCCCCCCCCCC(=O)N1C(=N)N(C)C(=O)C[C@@]1(C)c1ccc2sc3ccc(cc3c2c1)C#CC MTFXAMCNSZAEJY-QNGWXLTQSA-N 0.000 claims 2
- RGJTZWPFWJCREO-NRFANRHFSA-N (6S)-2-amino-3,6-dimethyl-6-(8-prop-1-ynyldibenzofuran-2-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C1=CC2=C(OC3=C2C=C(C=C3)C#CC)C=C1)C RGJTZWPFWJCREO-NRFANRHFSA-N 0.000 claims 2
- NUBQUFYKLJMNAI-NRFANRHFSA-N (6S)-2-amino-3,6-dimethyl-6-(8-prop-1-ynyldibenzothiophen-2-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C NUBQUFYKLJMNAI-NRFANRHFSA-N 0.000 claims 2
- LVNXCQXBORXCKI-MRXNPFEDSA-N (6S)-2-amino-3,6-dimethyl-6-[2-(5-prop-1-ynylpyridin-3-yl)ethenyl]-5H-pyrimidin-4-one Chemical compound N(=C\1/N[C@@](CC(N/1C)=O)(C=CC=1C=NC=C(C=1)C#CC)C)/[H] LVNXCQXBORXCKI-MRXNPFEDSA-N 0.000 claims 2
- DPXVUTUGNIOPIB-SFHVURJKSA-N (6S)-2-amino-3,6-dimethyl-6-[8-(trifluoromethyl)dibenzothiophen-2-yl]-5H-pyrimidin-4-one Chemical compound NC1=N[C@@](CC(N1C)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C(F)(F)F)C=C1)C DPXVUTUGNIOPIB-SFHVURJKSA-N 0.000 claims 2
- WOTUUUZFIWUIGA-QFIPXVFZSA-N (6S)-2-amino-3-(2,2-difluoroethyl)-6-methyl-6-(8-prop-1-ynyldibenzothiophen-2-yl)-5H-pyrimidin-4-one Chemical compound FC(CN1C(N[C@@](CC1=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C)=N)F WOTUUUZFIWUIGA-QFIPXVFZSA-N 0.000 claims 2
- MRVOXMFCXREREJ-QHCPKHFHSA-N (6S)-2-amino-3-(2-methoxyethyl)-6-methyl-6-(8-prop-1-ynyldibenzothiophen-2-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1CCOC)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C MRVOXMFCXREREJ-QHCPKHFHSA-N 0.000 claims 2
- AYIUXAXCNVTPTC-NRFANRHFSA-N (6S)-2-amino-6-(3-chloro-8-prop-1-ynyldibenzothiophen-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound ClC=1C(=CC2=C(SC3=C2C=C(C=C3)C#CC)C=1)[C@@]1(CC(N(C(N1)=N)C)=O)C AYIUXAXCNVTPTC-NRFANRHFSA-N 0.000 claims 2
- YMLPCTFQURLHKJ-NRFANRHFSA-N (6S)-2-amino-6-(3-fluoro-8-prop-1-ynyldibenzothiophen-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound FC=1C(=CC2=C(SC3=C2C=C(C=C3)C#CC)C=1)[C@@]1(CC(N(C(N1)=N)C)=O)C YMLPCTFQURLHKJ-NRFANRHFSA-N 0.000 claims 2
- SZDYSDZVHPBZKY-AWEZNQCLSA-N (6S)-2-amino-6-(7-hydroxy-1-benzofuran-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound OC1=CC=CC=2C=C(OC=21)[C@@]1(CC(N(C(N1)=N)C)=O)C SZDYSDZVHPBZKY-AWEZNQCLSA-N 0.000 claims 2
- MZYGPWCACIKSBZ-HNNXBMFYSA-N (6S)-2-amino-6-(7-methoxy-1-benzofuran-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound N=C1N[C@](CC(N1C)=O)(C)C=1OC2=C(C=1)C=CC=C2OC MZYGPWCACIKSBZ-HNNXBMFYSA-N 0.000 claims 2
- CQZXFAARULDROS-SFHVURJKSA-N (6S)-2-amino-6-(8-bromodibenzothiophen-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound CN1C(N)=N[C@@](C)(CC1=O)c1ccc2sc3ccc(Br)cc3c2c1 CQZXFAARULDROS-SFHVURJKSA-N 0.000 claims 2
- DENJMMZPAUEECX-NRFANRHFSA-N (6S)-2-amino-6-(8-cyclopropyldibenzothiophen-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound C1(CC1)C=1C=CC2=C(C3=C(S2)C=CC(=C3)[C@@]2(CC(N(C(N2)=N)C)=O)C)C=1 DENJMMZPAUEECX-NRFANRHFSA-N 0.000 claims 2
- QVSJMNTWKMFCER-NRFANRHFSA-N (6S)-2-amino-6-(9-fluoro-8-prop-1-ynyldibenzothiophen-2-yl)-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound FC1=C(C=CC2=C1C1=C(S2)C=CC(=C1)[C@@]1(CC(N(C(N1)=N)C)=O)C)C#CC QVSJMNTWKMFCER-NRFANRHFSA-N 0.000 claims 2
- SVJJCPJCDWYWOO-QFIPXVFZSA-N (6S)-2-amino-6-[8-(3-methoxyprop-1-ynyl)dibenzothiophen-2-yl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound COCC#Cc1ccc2sc3ccc(cc3c2c1)[C@]1(C)CC(=O)N(C)C(N)=N1 SVJJCPJCDWYWOO-QFIPXVFZSA-N 0.000 claims 2
- YLHQLLAHILJOTD-QFIPXVFZSA-N (6S)-2-amino-6-[8-(diethylamino)dibenzothiophen-2-yl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound CCN(CC)c1ccc2sc3ccc(cc3c2c1)[C@]1(C)CC(=O)N(C)C(N)=N1 YLHQLLAHILJOTD-QFIPXVFZSA-N 0.000 claims 2
- WTMDPYKCQOHOLJ-QHCPKHFHSA-N (8R)-8-methyl-6,6-dioxo-8-(8-prop-1-ynyldibenzothiophen-2-yl)-6lambda6-thia-9-azaspiro[4.5]dec-9-en-10-amine Chemical compound N=C1N[C@@](CS(C11CCCC1)(=O)=O)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C WTMDPYKCQOHOLJ-QHCPKHFHSA-N 0.000 claims 2
- VGOAETJNCUTHJV-IBGZPJMESA-N 8-[(4S)-2-amino-1,4-dimethyl-6-oxo-5H-pyrimidin-4-yl]dibenzothiophene-2-carbonitrile Chemical compound N=C1N(C(C[C@@](N1)(C)C=1C=CC2=C(C3=C(S2)C=CC(=C3)C#N)C=1)=O)C VGOAETJNCUTHJV-IBGZPJMESA-N 0.000 claims 2
- ROBXYRZNCQLYQR-IBGZPJMESA-N 8-[(4S)-2-amino-1,4-dimethyl-6-oxo-5H-pyrimidin-4-yl]dibenzothiophene-2-carboxamide Chemical compound CN1C(=O)C[C@](C)(N=C1N)c1ccc2sc3ccc(cc3c2c1)C(N)=O ROBXYRZNCQLYQR-IBGZPJMESA-N 0.000 claims 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims 2
- 201000010374 Down Syndrome Diseases 0.000 claims 2
- COEVKBSXSAZAMK-WIEQDCTASA-N FC=1C=CC2=C(NC3=C([C@H]4[C@@H]2C4)C=CC(=N3)[C@@]2(CS(C(C(N2)=N)(C)C)(=O)=O)C)C=1 Chemical compound FC=1C=CC2=C(NC3=C([C@H]4[C@@H]2C4)C=CC(=N3)[C@@]2(CS(C(C(N2)=N)(C)C)(=O)=O)C)C=1 COEVKBSXSAZAMK-WIEQDCTASA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 206010064930 age-related macular degeneration Diseases 0.000 claims 2
- 239000002585 base Substances 0.000 claims 2
- 125000005605 benzo group Chemical group 0.000 claims 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000002780 macular degeneration Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 238000007614 solvation Methods 0.000 claims 2
- OZBYFDJFHSRROP-BEFAXECRSA-N (3R)-3,6,6-trimethyl-1,1-dioxo-3-[(3R)-1-(4-prop-1-ynylpyridin-2-yl)pyrrolidin-3-yl]-2H-1,4-thiazin-5-amine Chemical compound N=C1N[C@@](CS(C1(C)C)(=O)=O)([C@H]1CN(CC1)C1=NC=CC(=C1)C#CC)C OZBYFDJFHSRROP-BEFAXECRSA-N 0.000 claims 1
- DSEZZJDMPJNZMG-QFIPXVFZSA-N (3R)-3-(4-fluoro-8-prop-1-ynyldibenzothiophen-2-yl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound CC#Cc1ccc2sc3c(F)cc(cc3c2c1)[C@]1(C)CS(=O)(=O)C(C)(C)C(N)=N1 DSEZZJDMPJNZMG-QFIPXVFZSA-N 0.000 claims 1
- ZAZXPGRZXPCRAZ-FQEVSTJZSA-N (3R)-3-[2-(1,3-dimethylpyrazol-4-yl)-1-benzothiophen-6-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound Cc1nn(C)cc1-c1cc2ccc(cc2s1)[C@]1(C)CS(=O)(=O)C(C)(C)C(N)=N1 ZAZXPGRZXPCRAZ-FQEVSTJZSA-N 0.000 claims 1
- XPYAKNDDKDOHOG-IBGZPJMESA-N (3R)-3-[2-(1,3-dimethylpyrazol-4-yl)indazol-5-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound CN1N=C(C(=C1)N1N=C2C=CC(=CC2=C1)[C@@]1(CS(C(C(N1)=N)(C)C)(=O)=O)C)C XPYAKNDDKDOHOG-IBGZPJMESA-N 0.000 claims 1
- ZFLXAFINRKTTKI-IBGZPJMESA-N (3R)-3-[2-(2,4-dimethyl-1,3-oxazol-5-yl)-3H-benzimidazol-5-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound Cc1nc(C)c(o1)-c1nc2ccc(cc2[nH]1)[C@]1(C)CS(=O)(=O)C(C)(C)C(N)=N1 ZFLXAFINRKTTKI-IBGZPJMESA-N 0.000 claims 1
- ONYARWWZRBUQFJ-IBGZPJMESA-N (3R)-3-[2-(2,4-dimethyl-1,3-oxazol-5-yl)indazol-5-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound Cc1nc(C)c(o1)-n1cc2cc(ccc2n1)[C@]1(C)CS(=O)(=O)C(C)(C)C(N)=N1 ONYARWWZRBUQFJ-IBGZPJMESA-N 0.000 claims 1
- MQOYPYYHBYQBBO-IBGZPJMESA-N (3R)-3-[2-(2,5-dimethylpyrazol-3-yl)-1,3-benzothiazol-6-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound Cc1cc(-c2nc3ccc(cc3s2)[C@]2(C)CS(=O)(=O)C(C)(C)C(N)=N2)n(C)n1 MQOYPYYHBYQBBO-IBGZPJMESA-N 0.000 claims 1
- RGLJDQPJDGJDEN-IBGZPJMESA-N (3R)-3-[2-(2,5-dimethylpyrazol-3-yl)-1,3-benzoxazol-6-yl]-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine Chemical compound Cc1cc(-c2nc3ccc(cc3o2)[C@]2(C)CS(=O)(=O)C(C)(C)C(N)=N2)n(C)n1 RGLJDQPJDGJDEN-IBGZPJMESA-N 0.000 claims 1
- YZFSPSBGKUKIIH-LJQANCHMSA-N (4R)-5,5-difluoro-4-methyl-4-(8-prop-1-ynyldibenzothiophen-2-yl)-6H-1,3-oxazin-2-amine Chemical compound FC1([C@](NC(OC1)=N)(C1=CC2=C(SC3=C2C=C(C=C3)C#CC)C=C1)C)F YZFSPSBGKUKIIH-LJQANCHMSA-N 0.000 claims 1
- AYJQECPHSZARBB-NRFANRHFSA-N (6R)-6-(7-fluoro-8-prop-1-ynyldibenzothiophen-2-yl)-6-methyl-4,4-dioxo-4lambda6-thia-7-azaspiro[2.5]oct-7-en-8-amine Chemical compound FC1=CC2=C(C3=C(S2)C=CC(=C3)[C@@]2(CS(C3(CC3)C(N2)=N)(=O)=O)C)C=C1C#CC AYJQECPHSZARBB-NRFANRHFSA-N 0.000 claims 1
- IXONLFNIVJIZSG-KRWDZBQOSA-N (6S)-2-amino-3,6-dimethyl-6-(3-prop-1-ynyl-1H-indol-5-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C=1C=C2C(=CNC2=CC=1)C#CC)C IXONLFNIVJIZSG-KRWDZBQOSA-N 0.000 claims 1
- LIGAUMZFOCJESW-SFHVURJKSA-N (6S)-2-amino-3,6-dimethyl-6-(3-prop-1-ynylquinolin-6-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C=1C=C2C=C(C=NC2=CC=1)C#CC)C LIGAUMZFOCJESW-SFHVURJKSA-N 0.000 claims 1
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| US10947223B2 (en) | 2016-12-15 | 2021-03-16 | Amgen Inc. | Substituted oxazines as beta-secretase inhibitors |
| 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 |
| GB201805816D0 (en) * | 2018-04-06 | 2018-05-23 | Ucb Biopharma Sprl | Therapeutic agents |
| CN109180670A (zh) * | 2018-09-17 | 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 |
| 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 |
| CN109796447B (zh) * | 2019-01-07 | 2020-03-13 | 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 |
| GB201906804D0 (en) | 2019-05-14 | 2019-06-26 | Ucb Biopharma Sprl | Therapeutic agents |
| CN114206856A (zh) | 2019-08-19 | 2022-03-18 | Ucb生物制药有限责任公司 | 抗疟疾的六氢嘧啶类似物 |
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| WO2023152042A1 (en) | 2022-02-08 | 2023-08-17 | UCB Biopharma SRL | Antimalarial hexahydropyrimidine analogues |
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| PT1699455E (pt) * | 2003-12-15 | 2013-08-27 | Merck Sharp & Dohme | Inibidores de protease de aspartilo heterocíclicos |
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| EP1802587A4 (en) * | 2004-10-15 | 2010-02-17 | Astrazeneca Ab | SUBSTITUTED AMINO BINDINGS AND THEIR APPLICATIONS |
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| EP2147914B1 (en) * | 2007-04-24 | 2014-06-04 | Shionogi&Co., Ltd. | Aminodihydrothiazine derivatives substituted with cyclic groups |
| EP2161271A1 (en) * | 2008-09-08 | 2010-03-10 | Università Degli Studi Di Milano - Bicocca | Alpha-carboline inhibitors of NMP-ALK, RET, and Bcr-Abl |
| UA108363C2 (uk) * | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| US8815881B2 (en) * | 2010-08-09 | 2014-08-26 | Hoffmann-La Roche Inc. | 1,4,5,6-tetrahydro-pyrimidin-2-ylamine compounds |
| 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 |
| JP2014514302A (ja) * | 2011-04-13 | 2014-06-19 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｂａｃｅ阻害薬としての５−置換されたイミノチアジン類およびそれのモノおよびジオキシド、組成物およびそれらの使用 |
| CN103596939A (zh) * | 2011-04-13 | 2014-02-19 | 默沙东公司 | 作为bace抑制剂的5-取代的亚氨基噻嗪类及其单和二氧化物、组合物及其应用 |
| RU2014111055A (ru) * | 2011-08-22 | 2015-09-27 | Мерк Шарп И Доум Корп. | 2-спирозамещенные иминотиазины и их моно- и диоксиды в качестве ингибиторов bace, композиции и их применение |
| WO2014062553A1 (en) * | 2012-10-17 | 2014-04-24 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| CA2825821A1 (en) * | 2013-08-28 | 2015-02-28 | Chiesi Farmaceutici S.P.A. | 1-phenylalkanecarboxylic acid derivatives for the treatment of alzheimer's disease and multiple sclerosis |
| CN104910238B (zh) | 2014-03-14 | 2017-08-11 | 中国科学院上海药物研究所 | 一类五环三萜类化合物及其在制备治疗阿尔兹海默病的药物中的用途 |
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2016
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- 2016-04-20 CA CA2979905A patent/CA2979905A1/en not_active Abandoned
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- 2016-04-20 MX MX2017013483A patent/MX2017013483A/es unknown
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- 2016-04-20 KR KR1020177032701A patent/KR20170139060A/ko not_active Withdrawn
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