CN103328454A - 作为bace1和/或bace2抑制剂的1，4噁嗪类 - Google Patents

作为bace1和/或bace2抑制剂的1，4噁嗪类 Download PDF

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Publication number
CN103328454A
CN103328454A CN201280005579XA CN201280005579A CN103328454A CN 103328454 A CN103328454 A CN 103328454A CN 201280005579X A CN201280005579X A CN 201280005579XA CN 201280005579 A CN201280005579 A CN 201280005579A CN 103328454 A CN103328454 A CN 103328454A
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CN
China
Prior art keywords
methyl
phenyl
dihydro
alkyl
oxazin
Prior art date
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Pending
Application number
CN201280005579XA
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English (en)
Chinese (zh)
Inventor
马瑟奥·安德烈尼
埃马努埃莱·加贝列里
沃尔夫冈·古帕
汉斯·希尔珀特
哈拉尔德·莫塞
亚历山大·V·迈韦格
罗伯特·纳尔基齐昂
约恩·鲍尔
玛斯米利亚诺·特拉瓦利
托马斯·沃尔特林
沃尔夫冈·沃斯特
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F Hoffmann La Roche AG
Siena Biotech SpA
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F Hoffmann La Roche AG
Siena Biotech SpA
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Filing date
Publication date
Application filed by F Hoffmann La Roche AG, Siena Biotech SpA filed Critical F Hoffmann La Roche AG
Publication of CN103328454A publication Critical patent/CN103328454A/zh
Pending legal-status Critical Current

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    • 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
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurosurgery (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Psychology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201280005579XA 2011-01-18 2012-01-16 作为bace1和/或bace2抑制剂的1，4噁嗪类 Pending CN103328454A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11151294.3 2011-01-18
EP11151294 2011-01-18
PCT/EP2012/050537 WO2012098064A1 (en) 2011-01-18 2012-01-16 1,4 oxazines as bace1 and/or bace2 inhibitors

Publications (1)

Publication Number Publication Date
CN103328454A true CN103328454A (zh) 2013-09-25

Family

ID=45491607

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201280005579XA Pending CN103328454A (zh) 2011-01-18 2012-01-16 作为bace1和/或bace2抑制剂的1，4噁嗪类

Country Status (10)

Country Link
US (1) US9242943B2 (https=)
EP (1) EP2665713A1 (https=)
JP (1) JP2014502982A (https=)
KR (1) KR20140014133A (https=)
CN (1) CN103328454A (https=)
BR (1) BR112013016360A2 (https=)
CA (1) CA2819158A1 (https=)
MX (1) MX2013007558A (https=)
RU (1) RU2013135678A (https=)
WO (1) WO2012098064A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103987710A (zh) * 2011-10-13 2014-08-13 诺华股份有限公司 新的*嗪衍生物及它们在治疗疾病中的应用

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CA2628074C (en) 2005-10-25 2014-01-14 Shionogi & Co., Ltd. Aminodihydrothiazine derivative
US8653067B2 (en) 2007-04-24 2014-02-18 Shionogi & Co., Ltd. Pharmaceutical composition for treating Alzheimer's disease
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
KR101324426B1 (ko) 2008-06-13 2013-10-31 시오노기세야쿠 가부시키가이샤 β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체
CN102186841A (zh) 2008-10-22 2011-09-14 盐野义制药株式会社 具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物
EP2485590B1 (en) 2009-10-08 2015-01-07 Merck Sharp & Dohme Corp. Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use
EP2485920B1 (en) 2009-10-08 2016-04-27 Merck Sharp & Dohme Corp. 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
MX2012006491A (es) 2009-12-11 2012-07-03 Shionogi & Co Derivados de oxazina.
MX339640B (es) 2010-06-09 2016-06-01 Janssen Pharmaceutica Nv * Derivados de 5, 6-dihidro-2h-[1, 4] oxazin-3-il-amina utiles como inhibidores de la beta-secretasa (bace).
JP5816630B2 (ja) 2010-10-29 2015-11-18 塩野義製薬株式会社 ナフチリジン誘導体
EP2634188A4 (en) 2010-10-29 2014-05-07 Shionogi & Co FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE
EP2655376B1 (en) 2010-12-22 2017-08-23 Janssen Pharmaceutica NV 5,6-DIHYDRO-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
CN103415519B (zh) 2011-03-01 2016-03-02 詹森药业有限公司 作为β-分泌酶(BACE)抑制剂有用的6，7-二氢-吡唑[1，5-a]吡嗪-4-基胺衍生物
AU2012224632B2 (en) 2011-03-09 2016-06-16 Janssen Pharmaceutica Nv 3,4-dihydro-pyrrolo[1,2-a]pyrazin-1-ylamine derivatives useful as inhibitors of beta-secretase (BACE)
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
EP2694521B1 (en) 2011-04-07 2015-11-25 Merck Sharp & Dohme Corp. Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use
US8883779B2 (en) 2011-04-26 2014-11-11 Shinogi & Co., Ltd. Oxazine derivatives and a pharmaceutical composition for inhibiting BACE1 containing them
CN103874496A (zh) 2011-08-22 2014-06-18 默沙东公司 作为bace抑制剂的2-螺-取代的亚氨基噻嗪类及其单和二氧化物、组合物及其用途
EP2788335B1 (en) * 2011-12-06 2016-04-13 Janssen Pharmaceutica, N.V. 5-(3-aminophenyl)-5-alkyl-5,6-dihydro-2h-[1,4]oxazin-3-amine derivatives for the treatment of disorders in which beta-secretase is involved
WO2014059185A1 (en) * 2012-10-12 2014-04-17 Amgen Inc. Amino - dihydrothiazine and amino - dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
EP2912035A4 (en) 2012-10-24 2016-06-15 Shionogi & Co DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY
MX368326B (es) 2013-06-12 2019-09-27 Janssen Pharmaceutica Nv Derivados de 4-amino-6-fenil-5,6-dihidroimidazo[1,5-a]pirazin-3(2h )-ona como inhibidores de beta-secretasa (bace).
KR102243134B1 (ko) 2013-06-12 2021-04-22 얀센 파마슈티카 엔.브이. 베타-세크레타제(bace) 저해제로서의 4-아미노-6-페닐-5,6-디하이드로이미다조[1,5-a]피라진 유도체
BR112015030597A2 (pt) 2013-06-12 2017-07-25 Janssen Pharmaceutica Nv derivados 4-amino-6-fenil-6,7-di-hidro[1,2,3]triazolo[1,5-a]pirazina como inibidores de beta-secretase (bace)
ES2768823T3 (es) 2014-12-18 2020-06-23 Janssen Pharmaceutica Nv Derivados de 2,3,4,5-tetrahidropiridin-6-amina y 3,4-dihidro-2H-pirrol-5-amina útiles como inhibidores de beta-secretasa
EP3271355B1 (en) 2015-03-20 2020-07-29 H. Hoffnabb-La Roche Ag Bace1 inhibitors

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US20070225267A1 (en) * 2004-09-21 2007-09-27 Broughton Howard B 3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors
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
CN101835771A (zh) * 2007-08-23 2010-09-15 诺瓦提斯公司 用作bace抑制剂的氨基苄基取代的环砜类

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UY32799A (es) * 2009-07-24 2011-02-28 Novartis Ag Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos
US8188079B2 (en) 2009-08-19 2012-05-29 Hoffman-La Roche Inc. 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines
US8673894B2 (en) * 2010-05-07 2014-03-18 Hoffmann-La Roche Inc. 2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine or 2,3,6,7-tetrahydro-[1,4]oxazepin-5-ylamine compounds
US8748418B2 (en) * 2011-03-18 2014-06-10 Hoffmann-La Roche Inc. 1,4-oxazepines as BACE1 and/or BACE2 inhibitors
US8785436B2 (en) * 2011-05-16 2014-07-22 Hoffmann-La Roche Inc. 1,3-oxazines as BACE 1 and/or BACE2 inhibitors

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
US20070225267A1 (en) * 2004-09-21 2007-09-27 Broughton Howard B 3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors
CN101835771A (zh) * 2007-08-23 2010-09-15 诺瓦提斯公司 用作bace抑制剂的氨基苄基取代的环砜类
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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103987710A (zh) * 2011-10-13 2014-08-13 诺华股份有限公司 新的*嗪衍生物及它们在治疗疾病中的应用

Also Published As

Publication number Publication date
CA2819158A1 (en) 2012-07-26
RU2013135678A (ru) 2015-02-27
KR20140014133A (ko) 2014-02-05
WO2012098064A1 (en) 2012-07-26
US20120184540A1 (en) 2012-07-19
BR112013016360A2 (pt) 2018-06-26
MX2013007558A (es) 2013-08-21
EP2665713A1 (en) 2013-11-27
US9242943B2 (en) 2016-01-26
JP2014502982A (ja) 2014-02-06

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