DK2297120T3 - Aminodihydrothiazine derivatives as bace inhibitors for the treatment of Alzheimer's disease - Google Patents
Aminodihydrothiazine derivatives as bace inhibitors for the treatment of Alzheimer's disease Download PDFInfo
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- DK2297120T3 DK2297120T3 DK09739419.1T DK09739419T DK2297120T3 DK 2297120 T3 DK2297120 T3 DK 2297120T3 DK 09739419 T DK09739419 T DK 09739419T DK 2297120 T3 DK2297120 T3 DK 2297120T3
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- Prior art keywords
- methyl
- compound
- dihydro
- equiv
- mmoles
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- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
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- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
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- 150000002576 ketones Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
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- YARKVSJAYDOCHK-MERQFXBCSA-N methyl (3s)-3-amino-3-(4-fluorophenyl)butanoate;hydrochloride Chemical compound Cl.COC(=O)C[C@](C)(N)C1=CC=C(F)C=C1 YARKVSJAYDOCHK-MERQFXBCSA-N 0.000 description 1
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- LJYVHAAXTPZBPB-UHFFFAOYSA-N n-[1-(3-bromophenyl)ethylidene]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)S(=O)N=C(C)C1=CC=CC(Br)=C1 LJYVHAAXTPZBPB-UHFFFAOYSA-N 0.000 description 1
- JAFLCHBHQRRYLT-SFHVURJKSA-N n-[[(2s)-2-(5-bromo-2-fluorophenyl)-4-hydroxybutan-2-yl]carbamothioyl]benzamide Chemical compound N([C@](CCO)(C)C=1C(=CC=C(Br)C=1)F)C(=S)NC(=O)C1=CC=CC=C1 JAFLCHBHQRRYLT-SFHVURJKSA-N 0.000 description 1
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- 125000004430 oxygen atom Chemical group O* 0.000 description 1
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- 239000008363 phosphate buffer Substances 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
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- 239000002243 precursor Substances 0.000 description 1
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- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 150000003384 small molecules Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 1
- ZEAFWQLZRQVLAO-FQEVSTJZSA-N tert-butyl n-[(4s)-4-(2,4-difluoro-5-pyrimidin-5-ylphenyl)-4-methyl-5,6-dihydro-1,3-thiazin-2-yl]carbamate Chemical compound C1CSC(NC(=O)OC(C)(C)C)=N[C@]1(C)C1=CC(C=2C=NC=NC=2)=C(F)C=C1F ZEAFWQLZRQVLAO-FQEVSTJZSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- CPMUYXLMGZRVEH-UHFFFAOYSA-N tributyl-(3-fluoropyrazin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CN=C1F CPMUYXLMGZRVEH-UHFFFAOYSA-N 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- BUJKNFNMGRYZBV-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+);hydrate Chemical compound O.[Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F BUJKNFNMGRYZBV-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
- C07D279/06—1,3-Thiazines; Hydrogenated 1,3-thiazines not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4988108P | 2008-05-02 | 2008-05-02 | |
| PCT/US2009/040589 WO2009134617A1 (en) | 2008-05-02 | 2009-04-15 | Aminodihydrothiazine derivatives as bace inhibitors for the treatment of alzheimer's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2297120T3 true DK2297120T3 (en) | 2015-10-12 |
Family
ID=40839645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09739419.1T DK2297120T3 (en) | 2008-05-02 | 2009-04-15 | Aminodihydrothiazine derivatives as bace inhibitors for the treatment of Alzheimer's disease |
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| US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| SG162790A1 (en) | 2005-06-14 | 2010-07-29 | Schering Corp | Aspartyl protease inhibitors |
| CN101394852A (zh) | 2005-06-14 | 2009-03-25 | 先灵公司 | 作为蛋白酶抑制剂的化合物的制备和用途 |
| AU2006307314C1 (en) | 2005-10-25 | 2011-08-25 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| PE20080155A1 (es) | 2006-06-12 | 2008-03-10 | Schering Corp | Compuestos heterociclicos como inhibidores de aspartil-proteasa |
| ES2476605T3 (es) | 2007-04-24 | 2014-07-15 | Shionogi & Co., Ltd. | Derivados de aminohidrotiazina sustituidos con grupos cíclicos |
| 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 |
| ES2548774T3 (es) * | 2008-01-18 | 2015-10-20 | Eisai R&D Management Co., Ltd. | Derivado de aminodihidrotiazina condensado |
| US8541427B2 (en) | 2008-04-22 | 2013-09-24 | Merck, Sharp & Dohme, Corp. | Phenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as BACE-1 inhibitors, compositions, and their use |
| TWI431004B (zh) * | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
| AU2009258496B8 (en) | 2008-06-13 | 2014-06-26 | Shionogi & Co., Ltd. | Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity |
| WO2010013794A1 (en) * | 2008-07-28 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Spiroaminodihydrothiazine derivatives |
| EP2324032B1 (en) | 2008-08-19 | 2014-10-01 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| CN102209721A (zh) | 2008-09-11 | 2011-10-05 | 安姆根有限公司 | 作为β-分泌酶调节剂的螺四环化合物及其使用方法 |
| KR20110076965A (ko) * | 2008-09-30 | 2011-07-06 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 신규한 축합 아미노 디하이드로티아진 유도체 |
| WO2010047372A1 (ja) | 2008-10-22 | 2010-04-29 | 塩野義製薬株式会社 | Ｂａｃｅ１阻害活性を有する２－アミノピリミジン－４－オンおよび２－アミノピリジン誘導体 |
| CN102348698B (zh) | 2009-03-13 | 2015-06-03 | 生命医药公司 | β-分泌酶的抑制剂 |
| GB0912778D0 (en) | 2009-07-22 | 2009-08-26 | Eisai London Res Lab Ltd | Fused aminodihydro-oxazine derivatives |
| GB0912777D0 (en) | 2009-07-22 | 2009-08-26 | Eisai London Res Lab Ltd | Fused aminodihydropyrimidone derivatives |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| AU2013234424B9 (en) * | 2009-10-08 | 2014-07-03 | Merck Sharp & Dohme Llc | Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
| US8563543B2 (en) | 2009-10-08 | 2013-10-22 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| US8569310B2 (en) | 2009-10-08 | 2013-10-29 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use |
| EP2485590B1 (en) | 2009-10-08 | 2015-01-07 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| EP2514747A4 (en) | 2009-12-09 | 2013-05-08 | Shionogi & Co | SUBSTITUTED AMINOTHIAZINE DERIVATIVE |
| JP5554346B2 (ja) * | 2009-12-09 | 2014-07-23 | 塩野義製薬株式会社 | 含硫黄複素環誘導体を含有するアルツハイマー症の治療用または予防用医薬組成物 |
| UA110467C2 (uk) | 2009-12-11 | 2016-01-12 | Шионогі Енд Ко., Лтд. | Похідні оксазину |
| WO2011077726A1 (ja) | 2009-12-24 | 2011-06-30 | 塩野義製薬株式会社 | ４－アミノ－１，３－チアジンまたはオキサジン誘導体 |
| EP2539322B1 (en) | 2010-02-24 | 2014-01-01 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| JP5584352B2 (ja) | 2010-03-15 | 2014-09-03 | アムジエン・インコーポレーテツド | β−セクレターゼ調節剤としてのアミノ−ジヒドロオキサジン系およびアミノ−ジヒドロチアジン系スピロ化合物ならびにそれらの医学的用途 |
| JP2013522305A (ja) | 2010-03-15 | 2013-06-13 | アムジエン・インコーポレーテツド | β−セクレターゼ調節剤としてのスピロ−四環式環化合物 |
| PH12012502377A1 (en) | 2010-06-09 | 2014-10-14 | Janssen Pharmaceutica Nv | 5,6-dihydro-2h-[1,4]oxazin-3-yl-amine derivatives useful as inhibitors of beta-secretase (bace) |
| US20130079349A1 (en) * | 2010-06-09 | 2013-03-28 | Janssen Pharmaceutica Nv | 5-amino-3,6-dihydro-1h-pyrazin-2-one derivatives useful as inhibitors of beta-secretase (bace) |
| EP2601197B1 (en) | 2010-08-05 | 2014-06-25 | Amgen Inc. | Amino-iso-indole, amino-aza-iso-indole, amino-dihydroisoquinoline and amino-benzoxazine compounds as beta-secretase modulators and methods of use |
| JP5766198B2 (ja) | 2010-10-29 | 2015-08-19 | 塩野義製薬株式会社 | 縮合アミノジヒドロピリミジン誘導体 |
| CN103261199A (zh) | 2010-10-29 | 2013-08-21 | 盐野义制药株式会社 | 萘啶衍生物 |
| WO2012071279A1 (en) | 2010-11-23 | 2012-05-31 | Amgen Inc. | Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use |
| NZ610948A (en) | 2010-12-22 | 2014-06-27 | Janssen Pharmaceutica Nv | 5,6-dihydro-imidazo[1,2-a]pyrazin-8-ylamine derivatives useful as inhibitors of beta-secretase (bace) |
| GB201100181D0 (en) | 2011-01-06 | 2011-02-23 | Eisai Ltd | Fused aminodihydrothiazine derivatives |
| GB201101139D0 (en) | 2011-01-21 | 2011-03-09 | Eisai Ltd | Fused aminodihydrothiazine derivatives |
| CA2814014A1 (en) | 2011-01-21 | 2012-07-26 | Branko MITASEV | Methods and compounds useful in the synthesis of fused aminodihydrothiazine derivatives |
| GB201101140D0 (en) | 2011-01-21 | 2011-03-09 | Eisai Ltd | Fused aminodihydrothiazine derivatives |
| US9346827B2 (en) | 2011-02-07 | 2016-05-24 | Amgen Inc. | 5-amino-oxazepine and 5-amino-thiazepane compounds as beta secretase antagonists and methods of use |
| WO2012112462A1 (en) | 2011-02-15 | 2012-08-23 | Amgen Inc. | Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use |
| JP5853033B2 (ja) | 2011-03-01 | 2016-02-09 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプＪａｎｓｓｅｎ Ｐｈａｒｍａｃｅｕｔｉｃａ Ｎａａｍｌｏｚｅ Ｖｅｎｎｏｏｔｓｃｈａｐ | β−セクレターゼ（ＢＡＣＥ）の阻害剤として有用な６，７−ジヒドロ−ピラゾロ［１，５−ａ］ピラジン−４−イルアミン誘導体 |
| BR112013022917A2 (pt) | 2011-03-09 | 2016-12-06 | Janssen Pharmaceutica Nv | derivados 3,4-dihidro-pirrolo[1,2-a]pirazino-1-ilamina úteis como inibidores de beta-secretase (bace) |
| US9145426B2 (en) | 2011-04-07 | 2015-09-29 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
| 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 |
| AU2012243329B2 (en) | 2011-04-13 | 2015-09-17 | Merck Sharp & Dohme Corp. | 5-substituted iminothiazines and their mono-and dioxides as BACE inhibitors,compositions,and their use |
| 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 |
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| WO2012147762A1 (ja) | 2011-04-26 | 2012-11-01 | 塩野義製薬株式会社 | ピリジン誘導体およびそれを含有するｂａｃｅ１阻害剤 |
| KR20140054295A (ko) | 2011-08-22 | 2014-05-08 | 머크 샤프 앤드 돔 코포레이션 | Bace 억제제로서의 2-스피로-치환된 이미노티아진 및 그의 모노- 및 디옥시드, 조성물 및 그의 용도 |
| JP2014526560A (ja) | 2011-09-21 | 2014-10-06 | アムジエン・インコーポレーテツド | β‐セクレターゼ調節因子としてのアミノオキサジン化合物およびアミノジヒドロチアジン化合物および使用方法 |
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