JP2020503294A5 - - Google Patents
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- Publication number
- JP2020503294A5 JP2020503294A5 JP2019531734A JP2019531734A JP2020503294A5 JP 2020503294 A5 JP2020503294 A5 JP 2020503294A5 JP 2019531734 A JP2019531734 A JP 2019531734A JP 2019531734 A JP2019531734 A JP 2019531734A JP 2020503294 A5 JP2020503294 A5 JP 2020503294A5
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- thiazine
- tautomer
- compound
- amino
- 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 83
- -1 2-propynyloxy Chemical group 0.000 claims 50
- 150000003839 salts Chemical class 0.000 claims 39
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 26
- QKFOHTNLZOIEHZ-UHFFFAOYSA-N 2h-1,3-thiazin-2-amine Chemical compound NC1SC=CC=N1 QKFOHTNLZOIEHZ-UHFFFAOYSA-N 0.000 claims 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 24
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 24
- 229920002554 vinyl polymer Polymers 0.000 claims 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 22
- 125000000217 alkyl group Chemical group 0.000 claims 16
- 125000003545 alkoxy group Chemical group 0.000 claims 9
- 125000001424 substituent group Chemical group 0.000 claims 9
- MSAMBWOENRGFFS-UHFFFAOYSA-N 4H-1,3-thiazine-6-carboxylic acid Chemical compound OC(=O)C1=CCN=CS1 MSAMBWOENRGFFS-UHFFFAOYSA-N 0.000 claims 8
- 206010012289 Dementia Diseases 0.000 claims 8
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 208000024827 Alzheimer disease Diseases 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 208000010877 cognitive disease Diseases 0.000 claims 4
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- OCOWEWOMRYUXLY-NZEFLHGSSA-N (4aR,7aS)-7a-[5-[(Z)-2-[5-(2,2-difluoroethoxy)pyrazin-2-yl]-2-fluoroethenyl]-2-fluorophenyl]-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine Chemical compound NC1=N[C@]2(CN(C[C@H]2CS1)C1=NC=C(F)C=N1)C1=C(F)C=CC(\C=C(/F)C2=CN=C(OCC(F)F)C=N2)=C1 OCOWEWOMRYUXLY-NZEFLHGSSA-N 0.000 claims 2
- ZOLASYMXTWTSAU-AIELCWNPSA-N 6-[(Z)-2-[3-[(4aR,7aS)-2-amino-6-(5-fluoro-4-methoxy-6-methylpyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-1-fluoroethenyl]pyridine-3-carbonitrile Chemical compound COC1=C(F)C(C)=NC(=N1)N1C[C@H]2CSC(N)=N[C@]2(C1)C1=C(F)C=CC(\C=C(/F)C2=CC=C(C=N2)C#N)=C1 ZOLASYMXTWTSAU-AIELCWNPSA-N 0.000 claims 2
- ATYAWJWVHNUXQF-DAISNLPVSA-N 6-[(Z)-2-[3-[(4aR,7aS)-2-amino-6-(5-fluoro-4-methoxypyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-1-fluoroethenyl]pyridine-3-carbonitrile Chemical compound COC1=C(F)C=NC(=N1)N1C[C@H]2CSC(N)=N[C@]2(C1)C1=C(F)C=CC(\C=C(/F)C2=CC=C(C=N2)C#N)=C1 ATYAWJWVHNUXQF-DAISNLPVSA-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
- 208000018737 Parkinson disease Diseases 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
- 230000002490 cerebral effect Effects 0.000 claims 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 230000007505 plaque formation Effects 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 206010048327 Supranuclear palsy Diseases 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 208000027061 mild cognitive impairment Diseases 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- WADGHWKXQZVKFK-UHFFFAOYSA-N thiazin-2-amine Chemical compound NN1SC=CC=C1 WADGHWKXQZVKFK-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662434719P | 2016-12-15 | 2016-12-15 | |
| US62/434,719 | 2016-12-15 | ||
| US201762570429P | 2017-10-10 | 2017-10-10 | |
| US62/570,429 | 2017-10-10 | ||
| PCT/US2017/066180 WO2018112084A1 (en) | 2016-12-15 | 2017-12-13 | Bicyclic thiazine and oxazine derivatives as beta-secretase inhibitors and methods of use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020503294A JP2020503294A (ja) | 2020-01-30 |
| JP2020503294A5 true JP2020503294A5 (enExample) | 2021-01-28 |
| JP7148518B2 JP7148518B2 (ja) | 2022-10-05 |
Family
ID=60888746
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019531734A Active JP7148518B2 (ja) | 2016-12-15 | 2017-12-13 | 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 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US11548903B2 (enExample) |
| EP (1) | EP3555106B1 (enExample) |
| JP (1) | JP7148518B2 (enExample) |
| AU (1) | AU2017376445B2 (enExample) |
| CA (1) | CA3047285A1 (enExample) |
| ES (1) | ES2910367T3 (enExample) |
| MA (1) | MA54101A (enExample) |
| MX (1) | MX394391B (enExample) |
| WO (1) | WO2018112084A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA110467C2 (uk) † | 2009-12-11 | 2016-01-12 | Шионогі Енд Ко., Лтд. | Похідні оксазину |
| US10947223B2 (en) | 2016-12-15 | 2021-03-16 | Amgen Inc. | Substituted oxazines as beta-secretase inhibitors |
| CA3047287A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use |
| 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 |
| 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. |
| WO2018112083A1 (en) | 2016-12-15 | 2018-06-21 | Amgen Inc. | Thiazine derivatives as beta-secretase inhibitors and methods of use |
Family Cites Families (60)
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|---|---|---|---|---|
| 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 |
| AU6383396A (en) | 1995-06-07 | 1996-12-30 | Athena Neurosciences, Inc. | Beta-secretase, antibodies to beta-secretase, and assays for detecting beta-secretase inhibition |
| KR100691601B1 (ko) | 1998-09-24 | 2007-03-09 | 파마시아 앤드 업존 캄파니 엘엘씨 | 알츠하이머병 세크레타제 |
| AU2006307314C1 (en) | 2005-10-25 | 2011-08-25 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| JP5383483B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | アルツハイマー症治療用医薬組成物 |
| ES2476605T3 (es) | 2007-04-24 | 2014-07-15 | Shionogi & Co., Ltd. | Derivados de aminohidrotiazina sustituidos con grupos cíclicos |
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| 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 |
| WO2010013794A1 (en) | 2008-07-28 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Spiroaminodihydrothiazine derivatives |
| KR20110076965A (ko) | 2008-09-30 | 2011-07-06 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 신규한 축합 아미노 디하이드로티아진 유도체 |
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| LT2912041T (lt) | 2012-10-26 | 2017-03-10 | Eli Lilly And Company | Tetrahidropiroltiazino dariniai kaip bace slopikliai |
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| AP2015008716A0 (en) | 2013-03-08 | 2015-09-30 | Amgen Inc | Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| 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 |
| JP6576433B2 (ja) | 2014-08-08 | 2019-09-18 | 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シクロプロピル縮合チアジン−2−アミン化合物及び使用方法 |
| EP3250035B1 (en) | 2015-04-21 | 2023-01-25 | 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 |
| 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 |
| 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 |
-
2017
- 2017-12-13 JP JP2019531734A patent/JP7148518B2/ja active Active
- 2017-12-13 AU AU2017376445A patent/AU2017376445B2/en active Active
- 2017-12-13 US US16/466,202 patent/US11548903B2/en active Active
- 2017-12-13 CA CA3047285A patent/CA3047285A1/en active Pending
- 2017-12-13 EP EP17822986.0A patent/EP3555106B1/en active Active
- 2017-12-13 ES ES17822986T patent/ES2910367T3/es active Active
- 2017-12-13 MA MA054101A patent/MA54101A/fr unknown
- 2017-12-13 MX MX2019007100A patent/MX394391B/es unknown
- 2017-12-13 WO PCT/US2017/066180 patent/WO2018112084A1/en not_active Ceased