ES2600636T3 - Spiro-[1,3]-oxazinas y spiro-[1,4]-oxazepinas como inhibidores de BACE1 y/o BACE2 - Google Patents
Spiro-[1,3]-oxazinas y spiro-[1,4]-oxazepinas como inhibidores de BACE1 y/o BACE2 Download PDFInfo
- Publication number
- ES2600636T3 ES2600636T3 ES12724116.4T ES12724116T ES2600636T3 ES 2600636 T3 ES2600636 T3 ES 2600636T3 ES 12724116 T ES12724116 T ES 12724116T ES 2600636 T3 ES2600636 T3 ES 2600636T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- group
- spiro
- hydrogen
- 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.)
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Classifications
-
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- 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
- 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
- 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
-
- 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
- C07D498/12—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 three hetero rings
- C07D498/20—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Compuesto de fórmula I:**Fórmula** en la que: V es -CR7aR7b-, W es -CR2aR2b-, X es -CR1aR1b-, -O-, -S- o -SO2-, Y -NH-C>=O-, Z se selecciona de entre el grupo que consiste de: i) heteroarilo, ii) heteroarilo sustituido con 1 a 4 sustituyentes seleccionados individualmente de entre R8, iii) arilo, y iv) arilo sustituido con 1 a 4 sustituyentes seleccionados individualmente de entre R8, R1a se selecciona de entre el grupo que consiste de: i) hidrógeno, ii) halógeno, y iii) alquilo-C1-6, R1b se selecciona de entre el grupo que consiste de: i) hidrógeno, ii) halógeno, y iii) alquilo-C1-6, R2a se selecciona de entre el grupo que consiste de: i) hidrógeno, y ii) alquilo-C1-6, R2b se selecciona de entre el grupo que consiste de: i) hidrógeno, ii) arilo, y iii) alquilo-C1-6, o R2a y R2b conjuntamente con el C al que se encuentran unidos forman un heterociclilo, R3 es F, R4 es F, R5 es H, R6 es H, R7a se selecciona de entre el grupo que consiste de: i) hidrógeno, y ii) alquilo-C1-6, R7b se selecciona de entre el grupo que consiste de: i) hidrógeno, y ii) alquilo-C1-6, R8 se selecciona de entre el grupo que consiste de: i) ciano, ii) ciano-alquilo C1-6, iii) halógeno, iv) halógeno-alcoxi C1-6, v) halógeno-alquilo C1-6, vi) alcoxi-C1-6, vii) alcoxi C1-6-alquilo C1-6, viii) alquinilo C2-6, y ix) alquilo-C1-6, n es 0 ó 1, m es 0 ó 1; p es 0 ó 1, o sales farmacéuticamente aceptables de los mismos.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11167835 | 2011-05-27 | ||
| EP11167835 | 2011-05-27 | ||
| PCT/EP2012/059688 WO2012163790A1 (en) | 2011-05-27 | 2012-05-24 | Spiro-[1,3]-oxazines and spiro-[1,4]-oxazepines as bace1 and/or bace2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2600636T3 true ES2600636T3 (es) | 2017-02-10 |
Family
ID=46177417
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12724116.4T Active ES2600636T3 (es) | 2011-05-27 | 2012-05-24 | Spiro-[1,3]-oxazinas y spiro-[1,4]-oxazepinas como inhibidores de BACE1 y/o BACE2 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US9079919B2 (es) |
| EP (1) | EP2714697B1 (es) |
| JP (1) | JP2014515382A (es) |
| KR (1) | KR20140048137A (es) |
| CN (1) | CN103596961B (es) |
| AU (1) | AU2012264875B2 (es) |
| BR (1) | BR112013030281A2 (es) |
| CA (1) | CA2833813A1 (es) |
| CL (1) | CL2013003372A1 (es) |
| CO (1) | CO6801773A2 (es) |
| CR (1) | CR20130580A (es) |
| EA (1) | EA024286B1 (es) |
| EC (1) | ECSP13013048A (es) |
| ES (1) | ES2600636T3 (es) |
| IL (1) | IL229334A (es) |
| MA (1) | MA35191B1 (es) |
| MX (1) | MX2013013910A (es) |
| PE (1) | PE20141205A1 (es) |
| PH (1) | PH12013502262A1 (es) |
| SG (1) | SG194835A1 (es) |
| UA (1) | UA111847C2 (es) |
| WO (1) | WO2012163790A1 (es) |
| ZA (1) | ZA201308395B (es) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2612854B1 (en) | 2005-10-25 | 2015-04-29 | Shionogi&Co., Ltd. | Aminothiazolidine and aminotetrahydrothiazepine derivatives as BACE 1 inhibitors |
| TW200902526A (en) | 2007-04-24 | 2009-01-16 | Shionogi & Amp Co Ltd | Aminodihydrothiazin derivative substituted with a cyclic group |
| WO2008133273A1 (ja) | 2007-04-24 | 2008-11-06 | Shionogi & Co., Ltd. | アルツハイマー症治療用医薬組成物 |
| WO2009151098A1 (ja) | 2008-06-13 | 2009-12-17 | 塩野義製薬株式会社 | βセクレターゼ阻害作用を有する含硫黄複素環誘導体 |
| JPWO2010047372A1 (ja) | 2008-10-22 | 2012-03-22 | 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 |
| WO2011044185A2 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| WO2011044187A1 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| WO2011044184A1 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| UA110467C2 (uk) | 2009-12-11 | 2016-01-12 | Шионогі Енд Ко., Лтд. | Похідні оксазину |
| CN103261199A (zh) | 2010-10-29 | 2013-08-21 | 盐野义制药株式会社 | 萘啶衍生物 |
| EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
| 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 |
| US9145426B2 (en) | 2011-04-07 | 2015-09-29 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
| WO2012147763A1 (ja) | 2011-04-26 | 2012-11-01 | 塩野義製薬株式会社 | オキサ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 |
| HK1208817A1 (en) | 2012-05-30 | 2016-03-18 | Comentis, Inc. | Chromane compounds |
| EP2912035A4 (en) | 2012-10-24 | 2016-06-15 | Shionogi & Co | DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY |
| EP2934534B1 (en) | 2012-12-21 | 2017-12-13 | Merck Sharp & Dohme Corp. | C5-spiro iminothiadiazine dioxides as bace inhibitors |
| CA2902212C (en) | 2013-03-01 | 2020-10-13 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| AU2014225604B2 (en) | 2013-03-08 | 2018-05-17 | Amgen Inc. | Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| US9725468B2 (en) | 2013-09-13 | 2017-08-08 | Merck Sharp & Dohme Corp. | C5-spiro iminothiazine dioxides as BACE inhibitors, compositions, and their use |
| AU2015301028B2 (en) | 2014-08-08 | 2019-09-26 | Amgen Inc. | Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| US10053453B2 (en) | 2014-10-07 | 2018-08-21 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| AU2016236402B2 (en) | 2015-03-20 | 2019-08-01 | F. Hoffmann-La Roche Ag | BACE1 inhibitors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA04010952A (es) | 2002-05-09 | 2005-01-25 | Pharmacia Corp | Compuestos de pirazolilo sustituidos para el tratamiento de la inflamacion. |
| TW200624426A (en) * | 2004-09-21 | 2006-07-16 | Lilly Co Eli | BACE inhibitors |
| US8211904B2 (en) * | 2005-07-18 | 2012-07-03 | Merck, Sharp & Dohme Corp. | Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease |
| EP2612854B1 (en) * | 2005-10-25 | 2015-04-29 | Shionogi&Co., Ltd. | Aminothiazolidine and aminotetrahydrothiazepine derivatives as BACE 1 inhibitors |
| AU2007293416A1 (en) | 2006-09-07 | 2008-03-13 | Merck & Co., Inc. | Spiropiperidine beta-secretase inhibitors for the treatment of Alzheimer's disease |
| WO2008133273A1 (ja) | 2007-04-24 | 2008-11-06 | Shionogi & Co., Ltd. | アルツハイマー症治療用医薬組成物 |
| CN102105475B (zh) * | 2008-07-28 | 2014-04-09 | 卫材R&D管理有限公司 | 螺氨基二氢噻嗪衍生物 |
| WO2010021680A2 (en) | 2008-08-19 | 2010-02-25 | Vitae Pharmaceuticals, Inc. | Inhibitors of beta-secretase |
| JPWO2010047372A1 (ja) * | 2008-10-22 | 2012-03-22 | 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 |
| WO2010073078A2 (en) | 2008-12-22 | 2010-07-01 | Orchid Research Laboratories Ltd. | Heterocyclic compounds as hdac inhibitors |
| US8461160B2 (en) * | 2009-05-08 | 2013-06-11 | Hoffmann-La Roche, Inc. | Dihydropyrimidinones |
| AR077328A1 (es) * | 2009-07-24 | 2011-08-17 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurologicos |
| US8188079B2 (en) * | 2009-08-19 | 2012-05-29 | Hoffman-La Roche Inc. | 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines |
| WO2011058763A1 (ja) * | 2009-11-13 | 2011-05-19 | 塩野義製薬株式会社 | アミノリンカーを有するアミノチアジンまたはアミノオキサジン誘導体 |
| 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 |
| AR080865A1 (es) * | 2010-03-31 | 2012-05-16 | Array Biopharma Inc | Derivados de espirotetrahidronaftaleno, composiciones farmaceuticas que los contienen, proceso de preparacion y uso de los mismos para tratar enfermedades neurodegenerativas,tal como alzheimer. |
| JP2012250933A (ja) * | 2011-06-03 | 2012-12-20 | Shionogi & Co Ltd | オキサジン誘導体を含有するアルツハイマー症治療用または予防用医薬組成物 |
-
2012
- 2012-05-21 US US13/476,094 patent/US9079919B2/en not_active Expired - Fee Related
- 2012-05-24 SG SG2013082607A patent/SG194835A1/en unknown
- 2012-05-24 CN CN201280025801.2A patent/CN103596961B/zh not_active Expired - Fee Related
- 2012-05-24 BR BR112013030281A patent/BR112013030281A2/pt not_active IP Right Cessation
- 2012-05-24 PH PH1/2013/502262A patent/PH12013502262A1/en unknown
- 2012-05-24 WO PCT/EP2012/059688 patent/WO2012163790A1/en not_active Ceased
- 2012-05-24 ES ES12724116.4T patent/ES2600636T3/es active Active
- 2012-05-24 PE PE2013002577A patent/PE20141205A1/es not_active Application Discontinuation
- 2012-05-24 CA CA2833813A patent/CA2833813A1/en not_active Abandoned
- 2012-05-24 AU AU2012264875A patent/AU2012264875B2/en not_active Expired - Fee Related
- 2012-05-24 EP EP12724116.4A patent/EP2714697B1/en not_active Not-in-force
- 2012-05-24 EA EA201391752A patent/EA024286B1/ru not_active IP Right Cessation
- 2012-05-24 UA UAA201315118A patent/UA111847C2/uk unknown
- 2012-05-24 KR KR1020137033959A patent/KR20140048137A/ko not_active Withdrawn
- 2012-05-24 MX MX2013013910A patent/MX2013013910A/es unknown
- 2012-05-24 JP JP2014513129A patent/JP2014515382A/ja active Pending
-
2013
- 2013-11-07 ZA ZA2013/08395A patent/ZA201308395B/en unknown
- 2013-11-07 IL IL229334A patent/IL229334A/en not_active IP Right Cessation
- 2013-11-07 CR CR20130580A patent/CR20130580A/es unknown
- 2013-11-13 CO CO13267226A patent/CO6801773A2/es not_active Application Discontinuation
- 2013-11-25 CL CL2013003372A patent/CL2013003372A1/es unknown
- 2013-11-25 EC ECSP13013048 patent/ECSP13013048A/es unknown
- 2013-12-18 MA MA36582A patent/MA35191B1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2012264875A1 (en) | 2013-10-31 |
| IL229334A0 (en) | 2014-01-30 |
| EA024286B1 (ru) | 2016-09-30 |
| CR20130580A (es) | 2013-12-09 |
| CO6801773A2 (es) | 2013-11-29 |
| CN103596961A (zh) | 2014-02-19 |
| MX2013013910A (es) | 2014-01-24 |
| IL229334A (en) | 2017-02-28 |
| WO2012163790A1 (en) | 2012-12-06 |
| US9079919B2 (en) | 2015-07-14 |
| NZ616817A (en) | 2015-12-24 |
| EA201391752A1 (ru) | 2014-04-30 |
| EP2714697B1 (en) | 2016-08-31 |
| CL2013003372A1 (es) | 2014-07-25 |
| PE20141205A1 (es) | 2014-09-22 |
| US20120302549A1 (en) | 2012-11-29 |
| KR20140048137A (ko) | 2014-04-23 |
| BR112013030281A2 (pt) | 2016-11-29 |
| CN103596961B (zh) | 2016-09-28 |
| UA111847C2 (uk) | 2016-06-24 |
| EP2714697A1 (en) | 2014-04-09 |
| ZA201308395B (en) | 2014-07-30 |
| JP2014515382A (ja) | 2014-06-30 |
| SG194835A1 (en) | 2013-12-30 |
| MA35191B1 (fr) | 2014-06-02 |
| ECSP13013048A (es) | 2014-01-31 |
| CA2833813A1 (en) | 2012-12-06 |
| PH12013502262A1 (en) | 2016-01-22 |
| AU2012264875B2 (en) | 2017-04-27 |
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