| 1089689-00-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• CAS: 1089689-00-8
• 化学式: C₁₆H₂₃FN₂O
• 分子量: 278.37
• InChiKey: PYCXXHJNEAXBNK-DETPVDSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  48.14
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 、 甲醇 、 三乙酰氧基硼氢化钠 、 原甲酸三乙酯 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Structure guided P1′ modifications of HEA derived β-secretase inhibitors for the treatment of Alzheimer’s disease

  摘要：

  The synthesis and SAR of a series of BACE-1 hydroxyethyl amine inhibitors containing substitutions on a spirocyclobutyl moiety is described. Selectivity against cathepsin D, a related aspartyl protease with potential off target toxicity, and improved microsomal stability is exemplified. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.060
• 作为产物：
  描述：

  (4'S)-6'-(2,2-dimethylpropyl)-3-hydroxy-3',4'-dihydrospirocyclobutane-1,2'-pyrano[2,3-b]pyridin-4'-amine 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 生成 、
  参考文献：
  名称：

  Structure guided P1′ modifications of HEA derived β-secretase inhibitors for the treatment of Alzheimer’s disease

  摘要：

  The synthesis and SAR of a series of BACE-1 hydroxyethyl amine inhibitors containing substitutions on a spirocyclobutyl moiety is described. Selectivity against cathepsin D, a related aspartyl protease with potential off target toxicity, and improved microsomal stability is exemplified. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.060

文献信息

• [EN] SUBSTITUTED HYDROXYETHYL AMINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE<br/>[FR] COMPOSÉS D'HYDROXYÉTHYLAMINE SUBSTITUÉE EN TANT QUE MODULATEURS DE BÊTA-SÉCRÉTASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2009064418A1

  公开（公告）日：2009-05-22

  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) I wherein R1, R2, R3, R4, R5, A1, A2, A3, A4, X and Z 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 (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

  本发明涵盖了一类新化合物，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）及相关疾病。在一种实施方案中，这些化合物具有一般的化学式（I），其中R1、R2、R3、R4、R5、A1、A2、A3、A4、X和Z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，如阿尔茨海默病（AD）、认知缺陷和损伤、精神分裂症和其他类似的中枢神经系统疾病。该发明还包括进一步的化学式II实施方案，以及用于制备化合物I和II的中间体和工艺。
• Substituted Pyrano [2,3-b] Pyridinamine compounds as beta-secretase modulators and methods of use
  申请人：Graceffa Russell

  公开号：US20100120774A1

  公开（公告）日：2010-05-13

  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 R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , X and Z 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 (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

  本发明包括一类新化合物，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）及相关疾病。在一个实施例中，这些化合物具有一般的化学式I，其中R1、R2、R3、R4、R5、A1、A2、A3、A4、X和Z在此处被定义。该发明还包括将这些化合物用于治疗与beta-分泌酶蛋白活性相关的疾病和情况的药物组合物。这些疾病包括阿尔茨海默病（AD）、认知缺陷和损伤、精神分裂症和其他类似的中枢神经系统疾病。该发明还包括化学式II的进一步实施例，以及有用于制备化学式I和II化合物的中间体和工艺。
• Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use
  申请人：Zhong Wenge

  公开号：US20090036478A1

  公开（公告）日：2009-02-05

  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 R 1a , R 1b , R 1c , B, W, R 3 , R 4 and R 5 are defined herein. In another embodiment, the invention provides compounds of general Formula II wherein A 1 , A 2 , A 3 , A 4 , R 1a , R 1b , R 1c , R 2 , R 4 , R 5 , W, X and Z 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 (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

  本发明涉及一类新化合物，适用于调节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R1a、R1b、R1c、B、W、R3、R4和R5在此定义。在另一种实施例中，本发明提供了一般式II的化合物，其中A1、A2、A3、A4、R1a、R1b、R1c、R2、R4、R5、W、X和Z在此定义。本发明还包括这些化合物在制药组合物中的使用，用于治疗与Beta-分泌酶蛋白活性相关的疾病和症状。这些疾病包括阿尔茨海默病（AD）、认知缺陷和损伤、精神分裂症和其他类似的中枢神经系统疾病。本发明还包括进一步的II式实施例、中间体和制备I式和II式化合物的有用工艺。
• SUBSTITUTED HYDROXYETHYL AMINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：ZHONG Wenge

  公开号：US20120220583A1

  公开（公告）日：2012-08-30

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase activity and for the treatment of diseases, including Alzheimer's disease (AD) and related CNS conditions, mediated thereby. In one embodiment, the compounds have a general Formula I or Formula II wherein R 1a-1c , B, R 3-5 and W of Formula I, and R 1a-1c , R 2-5 , A 1-4 , W, X, Z, m and n of Formula II are defined herein. The invention further provides compounds of Formula III and IV and sub-Formulas II-A-II-D and III-A-III-D. The compounds may be used in pharmaceutical compositions for treating, prophylactically or therapeutically, disorders related to the activity of beta-secretase protein, including without limitation, AD, cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions.

  本发明涉及一种新的化合物类别，用于调节Beta-分泌酶活性和治疗由此介导的疾病，包括阿尔茨海默病（AD）和相关的中枢神经系统疾病。在一种实施方案中，所述化合物具有通式I或通式II，其中式I中的R1a-1c、B、R3-5和W，式II中的R1a-1c、R2-5、A1-4、W、X、Z、m和n在此定义。本发明还提供了通式III和IV以及亚式II-A-II-D和III-A-III-D的化合物。所述化合物可用于制备药物组合物，用于预防或治疗与Beta-分泌酶蛋白活性相关的疾病，包括但不限于AD、认知缺陷和损伤、精神分裂症和其他类似的中枢神经系统疾病。
• SUBSTITUTED PYRANO [2,3-B] PYRIDINAMINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：GRACEFFA Russell

  公开号：US20100317668A1

  公开（公告）日：2010-12-16

  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 R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , X and Z 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 (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

  本发明涉及一类新的化合物，可用于调节Beta-秘酶酶活性，并用于治疗Beta-秘酶介导的疾病，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R1、R2、R3、R4、R5、A1、A2、A3、A4、X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，以治疗与beta-秘酶蛋白活性相关的疾病和症状，例如阿尔茨海默病（AD）、认知缺陷和损伤、精神分裂症和其他类似的中枢神经系统疾病。本发明还包括II式的进一步实施例、中间体和制备I式和II式化合物的有用过程。