(2R,4R)-tert-butyl 4-(allyloxy)-2-((1S,2S)-2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)pyrrolidine-1-carboxylate | 910447-68-6

• 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,4R)-tert-butyl 4-(allyloxy)-2-((1S,2S)-2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2R,4R)-2-[(1S,2S)-1-[tert-butyl(dimethyl)silyl]oxy-3-(3,5-difluorophenyl)-2-(phenylmethoxycarbonylamino)propyl]-4-prop-2-enoxypyrrolidine-1-carboxylate
• CAS: 910447-68-6
• 化学式: C₃₅H₅₀F₂N₂O₆Si
• 分子量: 660.874
• InChiKey: WQRWVTSVZMYNEQ-ITGKQZKFSA-N

物化性质

• 沸点：
  671.6±55.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.77
• 重原子数：
  46
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,4R)-tert-butyl 4-(allyloxy)-2-((1S,2S)-2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)pyrrolidine-1-carboxylate 在 Wilkinson's catalyst 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 (2R,4R)-tert-butyl 2-((1S,2S)-2-amino-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-hydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE)

  摘要：

  The synthesis, evaluation, and structure-activity relationships of a class of gamma-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of gamma-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.109
• 作为产物：
  描述：

  (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one 在 2,6-二甲基吡啶 、 三氟甲磺酸二丁硼 、 叠氮磷酸二苯酯 、 双氧水 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 (2R,4R)-tert-butyl 4-(allyloxy)-2-((1S,2S)-2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE)

  摘要：

  The synthesis, evaluation, and structure-activity relationships of a class of gamma-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of gamma-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.109

文献信息

• Novel gamma-lactams as beta-secretase inhibitors
  申请人：Thompson A. Lorin

  公开号：US20060046984A1

  公开（公告）日：2006-03-02

  There is provided a series of novel substituted gamma-lactams of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 4 , R 5 and R 6 as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型取代的γ-内酰胺，化学式为(I)或其立体异构体；或其药用盐，其中R1、R2、R4、R5和R6如本文所定义，它们的药用组合物和使用方法。这些新型化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地抑制Aβ肽的产生。本公开涉及对β-淀粉样蛋白产生相关的神经系统疾病的治疗有用的化合物，如阿尔茨海默病和其他受抗淀粉样活性影响的疾病。
• WO2006/99352
  申请人：——

  公开号：——

  公开（公告）日：——