7-bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine | 1335215-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 7-bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine
• 英文别名: 7-bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[14]oxazin]-5'-amine；7'-bromo-3'-chlorospiro[2,6-dihydro-1,4-oxazine-5,5'-chromeno[2,3-c]pyridine]-3-amine
• CAS: 1335215-72-9
• 化学式: C₁₅H₁₁BrClN₃O₂
• 分子量: 380.628
• InChiKey: HOQRIEAGKPSILD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine 在 二氧化碳 、 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 、 二乙醇胺 、 mineral oil 为溶剂， 20.0~100.0 ℃ 、10.0 MPa 条件下， 反应 2.08h， 生成 (S)-N-(7-bromo-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamide
  参考文献：
  名称：

  [EN] AMINO -DIHYDROOXAZINE AND AMINO - DIHYDROTHIAZINE SPIRO COMPOUNDS AS BETA - SECRETASE MODULATORS AND THEIR MEDICAL USE
  [FR] COMPOSÉS SPIRO DE L'AMINO-DIHYDROOXAZINE ET DE L'AMINO-DIHYDROTHIAZINE EN TANT QUE MODULATEURS DE LA BÉTA-SÉCRÉTASE ET UTILISATION MÉDICALE ASSOCIÉE

  摘要：

  本发明涉及一类新的化合物，用于调节Beta-分泌酶酶活性，治疗由Beta-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关病症。在一个实施例中，这些化合物具有一般的化学式（I）：其中化学式（I）中的A1、A2、A3、A4、A5、A6、R2、R7、X、Y和Z在此处定义。该发明还包括将这些化合物用于制备药物组合物，用于治疗与beta-分泌酶蛋白活性相关的疾病和病况，包括例如阿尔茨海默病、认知缺陷、认知障碍、精神分裂症以及其他与大脑斑块的形成和/或沉积相关的中枢神经系统病症。该发明还包括化学式（I）的进一步实施例，中间体和有助于制备化合物的过程。

  公开号：

  WO2011115928A1
• 作为产物：
  描述：

  2,5-二溴苯甲酸 在 盐酸 、 lithium aluminium tetrahydride 、 potassium tert-butylate 、 四丁基硫酸氢铵 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正庚烷 、 二氯甲烷 、 乙基苯 、 二甲基亚砜 为溶剂， 反应 9.91h， 生成 7-bromo-3-chloro-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine
  参考文献：
  名称：

  [EN] AMINO-OXAZINES AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
  [FR] COMPOSÉS D'AMINO-OXAZINES ET D'AMINO-DIHYDROTHIAZINE COMME MODULATEURS DE SÉCRÉTASE BÊTA ET PROCÉDÉS D'UTILISATION

  摘要：

  本发明涉及一类新的化合物，用于调节β-分泌酶酶活性，并用于治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）及相关病症。在一个实施例中，这些化合物具有一般的化学式I，其中化学式I中的A1、A2、A3、A4、A5、A6、L、R2、R7、X、Y和Z在此处定义。该发明还包括将这些化合物用于制备用于治疗与β-分泌酶蛋白活性相关的疾病和病症的药物组合物，包括例如阿尔茨海默病、认知缺陷、认知障碍、精神分裂症以及与大脑斑块的形成和/或沉积相关的其他中枢神经系统病症。该发明还涉及化学式I的进一步实施例、中间体和用于制备化合物的有用过程。

  公开号：

  WO2013044092A1

文献信息

• Amino-Oxazines and Amino-Dihydrothiazine Compounds as Beta-Secretase Modulators and Methods of Use
  申请人：CHEN Jian J.

  公开号：US20110251186A1

  公开（公告）日：2011-10-13

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新型化合物，用于调节Beta-分泌酶酶活性和治疗Beta-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施方式中，该化合物具有一般式I，其中式I中的A1、A2、A3、A4、A5、A6、R2、R7、X、Y和Z已在此定义。该发明还包括将这些化合物用于制备药物组合物，用于治疗与beta-分泌酶蛋白活性相关的疾病和症状，包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他与大脑斑块形成和/或沉积有关和/或由此引起的中枢神经系统疾病。该发明还包括式I的进一步实施方式、中间体和制备式I化合物的有用过程。
• AMINO-OXAZINES AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：US20140045828A1

  公开（公告）日：2014-02-13

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新的化合物，用于调节Beta-秘鲁酶酶活性和治疗Beta-秘鲁酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，该化合物具有通用的I式，其中I式中的A1、A2、A3、A4、A5、A6、R2、R7、X、Y和Z的定义在此处。本发明还包括将这些化合物用于制备用于治疗与Beta-秘鲁酶蛋白活性相关的疾病和病症的药物组合物，包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他与大脑斑块形成和/或沉积相关和/或由此引起的中枢神经系统疾病。本发明还包括公式I的进一步实施例、中间体和用于制备公式I化合物的方法。
• Amino-Oxazine and Amino-Dihydrothiazine Compounds as Beta-Secretase Modulators and Methods of Use
  申请人：AMGEN INC

  公开号：US20140296226A1

  公开（公告）日：2014-10-02

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , L, R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新型化合物类别，用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一个实施例中，该化合物具有一般式I，其中式I中的A1、A2、A3、A4、A5、A6、L、R2、R7、X、Y和Z在此定义。本发明还包括将这些化合物用于治疗与β-分泌酶蛋白活性相关的障碍和疾病的药物组合物，包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他与大脑斑块形成和/或沉积相关和/或由此引起的中枢神经系统疾病。本发明还包括式I的进一步实施例、中间体和用于制备式I化合物的过程。
• Amino-oxazines and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
  申请人：Chen Jian J.

  公开号：US08497264B2

  公开（公告）日：2013-07-30

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新的化合物，用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，所述化合物具有一般式I，其中式I中的A1、A2、A3、A4、A5、A6、R2、R7、X、Y和Z的定义如本文所述。本发明还包括使用这些化合物在药物组成物中治疗与β-分泌酶蛋白活性相关的疾病和症状，如阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他与大脑斑块形成和/或沉积相关和/或由其引起的中枢神经系统疾病。本发明还包括式I的进一步实施例、中间体和制备式I化合物的有用工艺。
• AMINO-OXAZINE AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：US20150307521A1

  公开（公告）日：2015-10-29

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , L, R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新型化合物类，用于调节Beta-分泌酶酶活性和治疗Beta-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，该化合物具有一般的I式，其中I式的A1、A2、A3、A4、A5、A6、L、R2、R7、X、Y和Z在此定义。本发明还包括将这些化合物用于制备药物组合物，用于治疗与Beta-分泌酶蛋白活性相关的障碍和疾病，例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他与大脑斑块形成和/或沉积相关和/或引起的中枢神经系统疾病。本发明还包括I式的进一步实施例、中间体和制备I式化合物的有用过程。