CA2867851A1 - Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof - Google Patents

Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof Download PDF

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Publication number
CA2867851A1
CA2867851A1 CA2867851A CA2867851A CA2867851A1 CA 2867851 A1 CA2867851 A1 CA 2867851A1 CA 2867851 A CA2867851 A CA 2867851A CA 2867851 A CA2867851 A CA 2867851A CA 2867851 A1 CA2867851 A1 CA 2867851A1
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CA
Canada
Prior art keywords
azaspiro
methyl
amino
oxa
undec
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.)
Abandoned
Application number
CA2867851A
Other languages
English (en)
French (fr)
Inventor
Ying-Zi Xu
Dean R. Artis
Simeon Bowers
Roy K. Hom
Hing L. Sham
Shendong Yuan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Elan Pharmaceuticals LLC
Original Assignee
Elan Pharmaceuticals LLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Elan Pharmaceuticals LLC filed Critical Elan Pharmaceuticals LLC
Publication of CA2867851A1 publication Critical patent/CA2867851A1/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/10—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
    • 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
    • C07D279/08—1,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
    • 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
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CA2867851A 2012-03-20 2013-03-20 Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof Abandoned CA2867851A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261613377P 2012-03-20 2012-03-20
US61/613,377 2012-03-20
US201261727248P 2012-11-16 2012-11-16
US61/727,248 2012-11-16
PCT/US2013/033177 WO2013142613A1 (en) 2012-03-20 2013-03-20 Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof

Publications (1)

Publication Number Publication Date
CA2867851A1 true CA2867851A1 (en) 2013-09-26

Family

ID=49223329

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2867851A Abandoned CA2867851A1 (en) 2012-03-20 2013-03-20 Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof

Country Status (8)

Country Link
US (4) US9493485B2 (enExample)
EP (1) EP2827857A4 (enExample)
JP (1) JP2015514073A (enExample)
AU (1) AU2013235117A1 (enExample)
BR (1) BR112014023384A8 (enExample)
CA (1) CA2867851A1 (enExample)
HK (1) HK1206597A1 (enExample)
WO (1) WO2013142613A1 (enExample)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ589590A (en) 2008-06-13 2012-05-25 Shionogi & Co Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity
WO2011071135A1 (ja) 2009-12-11 2011-06-16 塩野義製薬株式会社 オキサジン誘導体
US9540359B2 (en) 2012-10-24 2017-01-10 Shionogi & Co., Ltd. Dihydrooxazine or oxazepine derivatives having BACE1 inhibitory activity
TW201446758A (zh) * 2013-03-01 2014-12-16 Amgen Inc 作爲β－分泌酶抑制劑的全氟化５，６－二氫－４Ｈ－１，３－□－２－胺化合物及其用途
EP2964644B1 (en) 2013-03-08 2018-12-26 Amgen, Inc. Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use
PE20161225A1 (es) 2014-02-19 2016-12-04 H Lundbeck As 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer
WO2016001266A1 (en) 2014-07-04 2016-01-07 F. Hoffmann-La Roche Ag Fluoro-[1,3]oxazines as bace1 inhibitors
CN106795147B (zh) 2014-08-08 2020-09-22 美国安进公司 作为β-分泌酶抑制剂的环丙基稠合噻嗪-2-胺化合物和使用方法
CR20170187A (es) 2014-11-10 2018-02-01 H Lundbeck As 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer
JO3458B1 (ar) 2014-11-10 2020-07-05 H Lundbeck As 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1
MA40941A (fr) 2014-11-10 2017-09-19 H Lundbeck As 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1
TW201717948A (zh) 2015-08-10 2017-06-01 Ｈ 朗德貝克公司 包括給予２－胺基－３，５，５－三氟－３，４，５，６－四氫吡啶的聯合治療
WO2017025559A1 (en) 2015-08-12 2017-02-16 H. Lundbeck A/S 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridins as bace1 inhibitors
WO2018112081A1 (en) * 2016-12-15 2018-06-21 Amgen Inc. Oxazine derivatives as beta-secretase inhibitors and methods of use
JP7159161B2 (ja) 2016-12-15 2022-10-24 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誘導体および使用方法
ES2910367T3 (es) 2016-12-15 2022-05-12 Amgen Inc Derivados de tiazina y oxazina bicíclicos 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
AU2017376446B2 (en) 2016-12-15 2021-10-14 Amgen Inc. 1,4-thiazine dioxide and 1,2,4-thiadiazine dioxide derivatives as beta-secretase inhibitors and methods of use
CN109776295B (zh) * 2019-02-18 2021-10-01 浙江师范大学 一种邻位含二氟亚甲基的芳基碘化合物及制备方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0871720A2 (en) 1995-06-07 1998-10-21 Athena Neurosciences, Inc. Beta-secretase, antibodies to beta-secretase, and assays for detecting beta-secretase inhibition
US5744346A (en) 1995-06-07 1998-04-28 Athena Neurosciences, Inc. β-secretase
JP2009511589A (ja) 2005-10-12 2009-03-19 エラン ファーマシューティカルズ，インコーポレイテッド アリール−シクロプロピル誘導体のアスパルチルプロテアーゼ阻害剤を使用してアミロイドーシスを治療する方法
EP2612854B1 (en) 2005-10-25 2015-04-29 Shionogi&Co., Ltd. Aminothiazolidine and aminotetrahydrothiazepine derivatives as BACE 1 inhibitors
US7745484B2 (en) 2005-11-21 2010-06-29 Amgen Inc. Beta-secretase modulators and methods of use
EP1971598A1 (en) 2005-11-21 2008-09-24 Amgen Inc. Beta-secretase modulators and methods of use
JP5383484B2 (ja) 2007-04-24 2014-01-08 塩野義製薬株式会社 環式基で置換されたアミノジヒドロチアジン誘導体
EP2324032B1 (en) * 2008-08-19 2014-10-01 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
US20110065695A1 (en) 2009-09-11 2011-03-17 Jeremy Beauchamp Use of aminodihydrothiazines for the treatment or prevention of diabetes
US7964594B1 (en) * 2009-12-10 2011-06-21 Hoffmann-La Roche Inc. Amino oxazine derivatives
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

Also Published As

Publication number Publication date
US20150087826A1 (en) 2015-03-26
AU2013235117A1 (en) 2014-10-16
WO2013142613A1 (en) 2013-09-26
HK1206597A1 (en) 2016-01-15
BR112014023384A8 (pt) 2018-01-16
US20150307518A1 (en) 2015-10-29
BR112014023384A2 (pt) 2017-07-11
US20150087825A1 (en) 2015-03-26
EP2827857A1 (en) 2015-01-28
US9493485B2 (en) 2016-11-15
EP2827857A4 (en) 2016-03-30
US20160272654A1 (en) 2016-09-22
JP2015514073A (ja) 2015-05-18

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