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 | 676135-97-0

• 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: 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
• 英文别名: N-[(2S,3R)-1-(3,5-difluorophenyl)-4-[[(1S)-7-(2,2-dimethylpropyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]-3-hydroxybutan-2-yl]acetamide
• CAS: 676135-97-0
• 化学式: C₂₇H₃₆F₂N₂O₂
• 分子量: 458.592
• InChiKey: MQTCYFXKTJSLST-KKUQBAQOSA-N

物化性质

• 沸点：
  649.1±55.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 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-羟基苯并三唑 、 N-甲基吗啉氧化物 、 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 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

文献信息

• Acetyl 2-hydroxy-1, 3-diaminoalkanes
  申请人：——

  公开号：US20040180939A1

  公开（公告）日：2004-09-16

  Disclosed are compounds of the formula: 1 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.

  本发明揭示了公式1的化合物：其中变量Z、X、R15、R2、R3和Rc的定义如下。本发明所揭示的化合物是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方面有用。
• 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。
• US7244725B2
  申请人：——

  公开号：US7244725B2

  公开（公告）日：2007-07-17
• US7645780B2
  申请人：——

  公开号：US7645780B2

  公开（公告）日：2010-01-12
• Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Prime side chromane-containing inhibitors
  作者：Raymond A. Ng、Minghua Sun、Simeon Bowers、Roy K. Hom、Gary D. Probst、Varghese John、Lawrence Y. Fang、Michel Maillard、Andrea Gailunas、Louis Brogley、R. Jeffrey Neitz、Jay S. Tung、Michael A. Pleiss、Andrei W. Konradi、Hing L. Sham、Michael S. Dappen、Marc Adler、Nanhua Yao、Wes Zmolek、David Nakamura、Kevin P. Quinn、John-Michael Sauer、Michael P. Bova、Lany Ruslim、Dean R. Artis、Ted A. Yednock

  DOI：10.1016/j.bmcl.2013.06.006

  日期：2013.8

  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.