JP2018513191A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
Links
- 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
- FPXDGVFYCLFFMH-SFHVURJKSA-N (6S)-2-amino-3,6-dimethyl-6-(6-prop-1-ynylquinolin-3-yl)-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C=1C=NC2=CC=C(C=C2C=1)C#CC)C FPXDGVFYCLFFMH-SFHVURJKSA-N 0.000 claims 1
- ODHJGITVUNMHKJ-NRFANRHFSA-N (6S)-2-amino-3,6-dimethyl-6-(8-propyldibenzothiophen-2-yl)-5H-pyrimidin-4-one Chemical compound CCCc1ccc2sc3ccc(cc3c2c1)[C@]1(C)CC(=O)N(C)C(N)=N1 ODHJGITVUNMHKJ-NRFANRHFSA-N 0.000 claims 1
- JGKZBAGAWLKILO-IBGZPJMESA-N (6S)-2-amino-3,6-dimethyl-6-[2-(2-methylpent-3-yn-2-yl)-1,3-benzoxazol-5-yl]-5H-pyrimidin-4-one Chemical compound N=C1N[C@@](CC(N1C)=O)(C=1C=CC2=C(N=C(O2)C(C)(C#CC)C)C=1)C JGKZBAGAWLKILO-IBGZPJMESA-N 0.000 claims 1
- XHXHCGNZWLJHOF-LGTGAQBVSA-N (6S)-2-amino-3,6-dimethyl-6-[4-[1-(4-prop-1-ynylimidazol-1-yl)ethyl]phenyl]-5H-pyrimidin-4-one Chemical compound CC#Cc1cn(cn1)C(C)c1ccc(cc1)[C@]1(C)CC(=O)N(C)C(N)=N1 XHXHCGNZWLJHOF-LGTGAQBVSA-N 0.000 claims 1
- HQSGTTCAOMYPLM-ROUUACIJSA-N (6S)-2-amino-6-[2-[(2S)-2-hydroxypent-3-yn-2-yl]-1,3-benzoxazol-5-yl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound CC#C[C@](C)(O)c1nc2cc(ccc2o1)[C@]1(C)CC(=O)N(C)C(N)=N1 HQSGTTCAOMYPLM-ROUUACIJSA-N 0.000 claims 1
- ADRBAIMQONCBAL-DEOSSOPVSA-N (6S)-2-amino-6-[2-chloro-5-[(3-prop-1-ynylquinolin-8-yl)amino]phenyl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound ClC1=C(C=C(C=C1)NC=1C=CC=C2C=C(C=NC=12)C#CC)[C@@]1(CC(N(C(N1)=N)C)=O)C ADRBAIMQONCBAL-DEOSSOPVSA-N 0.000 claims 1
- AXQJQWUNKXWZNR-NRFANRHFSA-N (6S)-2-amino-6-[2-chloro-5-[(5-prop-1-ynylpyridin-2-yl)methylamino]phenyl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound CC#Cc1ccc(CNc2ccc(Cl)c(c2)[C@]2(C)CC(=O)N(C)C(N)=N2)nc1 AXQJQWUNKXWZNR-NRFANRHFSA-N 0.000 claims 1
- BFVLYKCUPVBWNZ-QFIPXVFZSA-N (6S)-2-amino-6-[2-chloro-5-[(6-prop-1-ynylthieno[3,2-b]pyridin-3-yl)amino]phenyl]-3,6-dimethyl-5H-pyrimidin-4-one Chemical compound ClC1=C(C=C(C=C1)NC1=CSC=2C1=NC=C(C=2)C#CC)[C@@]1(CC(N(C(N1)=N)C)=O)C BFVLYKCUPVBWNZ-QFIPXVFZSA-N 0.000 claims 1
- 208000000044 Amnesia Diseases 0.000 claims 1
- 206010059245 Angiopathy Diseases 0.000 claims 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 208000010412 Glaucoma Diseases 0.000 claims 1
- 208000026139 Memory disease Diseases 0.000 claims 1
- 208000029578 Muscle disease Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- 206010036631 Presenile dementia Diseases 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
- 206010044688 Trisomy 21 Diseases 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 1
- BQELHDAACQFRIT-OAHLLOKOSA-N but-2-ynyl 1-[(4S)-2-amino-1,4-dimethyl-6-oxo-5H-pyrimidin-4-yl]pyrrole-3-carboxylate Chemical compound N=C1N(C(C[C@@](N1)(C)N1C=C(C=C1)C(=O)OCC#CC)=O)C BQELHDAACQFRIT-OAHLLOKOSA-N 0.000 claims 1
- YQTRLIHPFAZDCC-HNNXBMFYSA-N but-2-ynyl 3-[(4S)-2-amino-1,4-dimethyl-6-oxo-5H-pyrimidin-4-yl]pyrrole-1-carboxylate Chemical compound N=C1N(C(C[C@@](N1)(C)C1=CN(C=C1)C(=O)OCC#CC)=O)C YQTRLIHPFAZDCC-HNNXBMFYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 1
- 230000006984 memory degeneration Effects 0.000 claims 1
- 208000023060 memory loss Diseases 0.000 claims 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 230000009529 traumatic brain injury Effects 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562150715P | 2015-04-21 | 2015-04-21 | |
| US62/150,715 | 2015-04-21 | ||
| US201662274791P | 2016-01-05 | 2016-01-05 | |
| US62/274,791 | 2016-01-05 | ||
| PCT/US2016/028502 WO2016172255A1 (en) | 2015-04-21 | 2016-04-20 | Compounds and their use as bace1 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018513191A JP2018513191A (ja) | 2018-05-24 |
| JP2018513191A5 true JP2018513191A5 (enExample) | 2019-05-30 |
| JP6765681B2 JP6765681B2 (ja) | 2020-10-07 |
Family
ID=57144237
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017555545A Active JP6765681B2 (ja) | 2015-04-21 | 2016-04-20 | Ｂａｃｅ１阻害剤としての化合物およびそれらの使用 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10870635B2 (enExample) |
| EP (1) | EP3250035B1 (enExample) |
| JP (1) | JP6765681B2 (enExample) |
| KR (1) | KR20170139060A (enExample) |
| CN (1) | CN107613771B (enExample) |
| AU (1) | AU2016250519A1 (enExample) |
| BR (1) | BR112017022568A2 (enExample) |
| CA (1) | CA2979905A1 (enExample) |
| ES (1) | ES2942308T3 (enExample) |
| MX (1) | MX2017013483A (enExample) |
| SG (1) | SG11201708027XA (enExample) |
| TW (1) | TWI680971B (enExample) |
| WO (1) | WO2016172255A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2017376441B2 (en) | 2016-12-15 | 2021-10-14 | Amgen Inc. | Oxazine derivatives as beta-secretase inhibitors and methods of use |
| MX388697B (es) | 2016-12-15 | 2025-03-20 | Amgen Inc | Derivados de tiazina como inhibidores de beta-secretasa y metodos de uso. |
| MX386618B (es) | 2016-12-15 | 2025-03-19 | Amgen Inc | Derivados de tiazina condensados con ciclopropilo como inhibidores de beta-secretasa y métodos de uso. |
| AU2017376445B2 (en) | 2016-12-15 | 2021-09-30 | 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. |
| 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 |
| US20220289685A1 (en) | 2019-08-19 | 2022-09-15 | UCB Biopharma SRL | Antimalarial hexahydropyrimidine analogues |
| GB202010606D0 (en) | 2020-07-10 | 2020-08-26 | Ucb Biopharma Sprl | Therapeutic agents |
| MX2023014819A (es) | 2021-06-14 | 2024-03-21 | Scorpion Therapeutics Inc | Derivados de la urea que pueden ser utilizados para tratar el cancer. |
| EP4476201A1 (en) | 2022-02-08 | 2024-12-18 | UCB Biopharma SRL | Antimalarial hexahydropyrimidine analogues |
| WO2026046157A1 (zh) * | 2024-08-27 | 2026-03-05 | 上海汇伦医药股份有限公司 | 苯并杂芳环类化合物、含其的组合物及其应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| CA2548388A1 (en) * | 2003-12-15 | 2005-06-30 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US20090221579A1 (en) | 2004-10-15 | 2009-09-03 | Jeffrey Scott Albert | Substituted Amino-Compounds and Uses Thereof |
| ES2537898T3 (es) * | 2005-10-25 | 2015-06-15 | Shionogi & Co., Ltd. | Derivados de aminotiazolidina y aminotetrahidrotiazepina como inhibidores de BACE 1 |
| CA2653650A1 (en) | 2006-06-12 | 2007-12-21 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| AU2008245082B8 (en) * | 2007-04-24 | 2012-09-13 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivatives substituted with a cyclic group |
| 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 |
| EP2694521B1 (en) | 2011-04-07 | 2015-11-25 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| WO2012138734A1 (en) * | 2011-04-07 | 2012-10-11 | Merck Sharp & Dohme Corp. | C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| BR112013026341A2 (pt) * | 2011-04-13 | 2019-09-24 | Merck Sharp & Dohe Corp. | composto, composição farmacêutica, e, método para tratar, prevenir e/ou atrasar o início de uma doença ou patologia |
| 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 |
-
2016
- 2016-04-20 JP JP2017555545A patent/JP6765681B2/ja active Active
- 2016-04-20 CA CA2979905A patent/CA2979905A1/en not_active Abandoned
- 2016-04-20 ES ES16783796T patent/ES2942308T3/es active Active
- 2016-04-20 US US15/568,449 patent/US10870635B2/en active Active
- 2016-04-20 CN CN201680021454.4A patent/CN107613771B/zh active Active
- 2016-04-20 KR KR1020177032701A patent/KR20170139060A/ko not_active Withdrawn
- 2016-04-20 AU AU2016250519A patent/AU2016250519A1/en not_active Abandoned
- 2016-04-20 EP EP16783796.2A patent/EP3250035B1/en active Active
- 2016-04-20 BR BR112017022568A patent/BR112017022568A2/pt not_active Application Discontinuation
- 2016-04-20 SG SG11201708027XA patent/SG11201708027XA/en unknown
- 2016-04-20 MX MX2017013483A patent/MX2017013483A/es unknown
- 2016-04-20 WO PCT/US2016/028502 patent/WO2016172255A1/en not_active Ceased
- 2016-04-21 TW TW105112413A patent/TWI680971B/zh active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102359836B1 (ko) | 시클로프로판아민 화합물 및 이의 용도 | |
| JP6114809B2 (ja) | ｍＧｌｕＲ２−陰性アロステリック調節因子としてのキノリンカルボキサミドおよびキノリンカルボニトリル誘導体、組成物、およびその使用 | |
| AU2024203831A1 (en) | Aminothiazole compounds as c-Kit inhibitors | |
| ES2350460T3 (es) | Derivados de 3-aza-biciclo[3.1.0]hexano. | |
| Zhang et al. | Design, synthesis and biological evaluation of novel 1, 2, 4-triazolo [3, 4-b][1, 3, 4] thiadiazines bearing furan and thiophene nucleus | |
| JP2012511054A5 (enExample) | ||
| CA2800405C (en) | Antidepressant, neuroprotectant, amyloid .beta. deposition inhibitor or age retardant containing heterocyclic compound having specific structure | |
| EP3692028A1 (en) | Inhibiting ubiquitin specific peptidase 30 | |
| WO2012066578A2 (en) | Substituted 4-(selenophen-2(or 3)-ylamino)pyrimidine compounds and methods of use thereof | |
| KR20120115350A (ko) | 치료 화합물 및 관련된 사용 방법 | |
| ES2762938T3 (es) | Inhibidores de Kv1.3 y su aplicación médica | |
| KR20090050094A (ko) | 세린-트레오닌 단백질 키나제 및 ｐａｒｐ 조절제 | |
| JP2018501315A5 (enExample) | ||
| HRP20140451T1 (hr) | Derivati izoksazola i njihova uporaba kao pojaäśivaäśa metabotropnih glutamatnih receptora | |
| JP6698633B2 (ja) | 複素環化合物 | |
| JP4354106B2 (ja) | 縮合チオフェン化合物およびその医薬用途 | |
| JP2009541404A5 (enExample) | ||
| JP2017513887A5 (enExample) | ||
| JP2010500334A5 (enExample) | ||
| JPWO1999011647A1 (ja) | 縮合チオフェン化合物およびその医薬用途 | |
| JP2018510203A5 (enExample) | ||
| WO2018213813A2 (en) | Psychotropic agents and uses thereof | |
| US9650377B2 (en) | Diazepinone derivatives | |
| US9611276B2 (en) | Imidazo bicyclic iminium compounds as antitumor agents | |
| JP2013227299A5 (enExample) |