(S)-N-(2-amino-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9'-xanthen]-7'-yl)-5-chloropicolinamide | 1428632-68-1

• 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: (S)-N-(2-amino-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9'-xanthen]-7'-yl)-5-chloropicolinamide
• 英文别名: N-(4S)-(2-amino-5'-fluoro-7'-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9'-xanthen]-2'-yl)-5-chloro-2-pyridinecarboxamide；N-[(4S)-2-amino-5'-fluoro-7'-methoxyspiro[5,6-dihydro-1,3-oxazine-4,9'-xanthene]-2'-yl]-5-chloropyridine-2-carboxamide
• CAS: 1428632-68-1
• 化学式: C₂₃H₁₈ClFN₄O₄
• 分子量: 468.872
• InChiKey: ZHIZQQIASYDJIR-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-7'-bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine 在 copper(l) iodide 、 sodium azide 、 (1S,2S)-(+)-1,2-环己二胺 、 水 、 sodium ascorbate 、 三乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 8.03h， 生成 (S)-N-(2-amino-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9'-xanthen]-7'-yl)-5-chloropicolinamide
  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-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-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
  申请人：AMGEN INC.

  公开号：US09296759B2

  公开（公告）日：2016-03-29

  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 A1, A2, A3, A4, A5, A6, L, 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，所述化合物具有一般的I式，其中I式中的A1、A2、A3、A4、A5、A6、L、R2、R7、X、Y和Z在此定义。本发明还包括这些化合物在药物组合物中的使用，用于治疗与Beta-分泌酶蛋白活性相关的障碍和疾病，包括例如阿尔茨海默病、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/或由此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、中间体和用于制备I式化合物的有用工艺。
• US9296759B2
  申请人：——

  公开号：US9296759B2

  公开（公告）日：2016-03-29
• US9777019B2
  申请人：——

  公开号：US9777019B2

  公开（公告）日：2017-10-03
• [EN] AMINO-OXAZINES AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE<br/>[FR] COMPOSÉS D'AMINO-OXAZINES ET D'AMINO-DIHYDROTHIAZINE COMME MODULATEURS DE SÉCRÉTASE BÊTA ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2013044092A1

  公开（公告）日：2013-03-28

  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, L, 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，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。