tert-butyl (2R,4R)-2-((1S,2S)-1-((tert-butyldimethylsilyl)oxy)-3-(3,5-difluorophenyl)-2-((S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)propanamido)propyl)-4-propoxypyrrolidine-1-carboxylate | 1345706-16-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (2R,4R)-2-((1S,2S)-1-((tert-butyldimethylsilyl)oxy)-3-(3,5-difluorophenyl)-2-((S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)propanamido)propyl)-4-propoxypyrrolidine-1-carboxylate
• CAS: 1345706-16-2
• 化学式: C₃₈H₆₃F₂N₃O₆Si
• 分子量: 724.017
• InChiKey: YPLRSHDHQRNGOS-KDBVRDCOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.47
• 重原子数：
  50.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  97.41
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,4R)-2-((1S,2S)-1-((tert-butyldimethylsilyl)oxy)-3-(3,5-difluorophenyl)-2-((S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)propanamido)propyl)-4-propoxypyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (S)-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)propanoate
  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：

  在 N-甲基吗啉 、 三乙基硅烷 、 HATU 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (2R,4R)-2-((1S,2S)-1-((tert-butyldimethylsilyl)oxy)-3-(3,5-difluorophenyl)-2-((S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)propanamido)propyl)-4-propoxypyrrolidine-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