(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-ol | 865472-25-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-ol
• CAS: 865472-25-9
• 化学式: C₂₅H₃₄F₂N₂O
• 分子量: 416.555
• InChiKey: OEEYUZPPARUOSD-KMDXXIMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  58.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-ol 、 溶剂黄146 在 1-羟基苯并三唑 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 为溶剂， 生成 N-(1S,2R)-{1-(3,5-difluoro-benzyl)-3-[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydro-naphthalen-1-ylamino]-2-hydroxypropyl}-acetamide
  参考文献：
  名称：

  Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Prime side chromane-containing inhibitors

  摘要：

  The structure structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.006
• 作为产物：
  描述：

  (R)-(-)-1,2,3,4-四氢-1-萘酚 在 盐酸 、 lithium aluminium tetrahydride 、 叠氮磷酸二苯酯 、 Pd(1,1-bis(diphenylphosphino)ferrocene)₂Cl₂ 、 碘 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 mercury(II) oxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 生成 (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-ol
  参考文献：
  名称：

  Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Prime side chromane-containing inhibitors

  摘要：

  The structure structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.006

文献信息

• Methods of treatment of amyloidosis using bi-cyclic aspartyl protease inhibitors
  申请人：John Varghese

  公开号：US20050239832A1

  公开（公告）日：2005-10-27

  The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

  本发明涉及新型化合物和治疗与淀粉样变性相关的疾病、紊乱和状况的方法。淀粉样变性是指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和状况的集合。
• Acetyl 2-hydroxy-1, 3-diaminoalkanes
  申请人：John Varghese

  公开号：US20070293483A1

  公开（公告）日：2007-12-20

  Disclosed are compounds of the formula: where variables Z, X, R 15 , R 2 , R 3 , and R c are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal.

  本发明涉及以下式子的化合物：其中变量Z、X、R15、R2、R3和Rc在此定义。本发明揭示的化合物是β-分泌酶酶的抑制剂，因此在治疗老年痴呆症和其他以A beta肽在哺乳动物中沉积为特征的疾病中有用。
• ACETYL 2-HYDROXY-1,3-DIAMINOALKANES
  申请人：John Varghese

  公开号：US20100145056A1

  公开（公告）日：2010-06-10

  Disclosed are compounds of the formula: where variables Z, X, R 15 , R 2 , R 3 , and R c are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal.

  公开了以下式子的化合物：其中变量Z，X，R15，R2，R3和R4在此处定义。本文所披露的化合物是β-分泌酶酶的抑制剂，因此在治疗阿尔茨海默病和其他以A beta肽在哺乳动物中沉积为特征的疾病中有用。
• METHODS OF TREATMENT OF AMYLOIDOSIS USING BI-CYCLIC ASPARTYL PROTEASE INHIBITORS
  申请人：ELAN PHARMACEUTICALS, INC.

  公开号：EP1734961A2

  公开（公告）日：2006-12-27
• US7244725B2
  申请人：——

  公开号：US7244725B2

  公开（公告）日：2007-07-17