2-((2S,4R)-1-((R,Z)-1-(4-chlorophenyl)-4-methylpent-2-enyl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid | 1404070-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-((2S,4R)-1-((R,Z)-1-(4-chlorophenyl)-4-methylpent-2-enyl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid
• 英文别名: 2-[(2S,4R)-1-[(Z,1R)-1-(4-chlorophenyl)-4-methylpent-2-enyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetic acid
• CAS: 1404070-14-9
• 化学式: C₂₆H₂₉ClF₃NO₂
• 分子量: 479.97
• InChiKey: QKNOOOPWQYWKGA-RPBCGYHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-甲基-1-丁炔 在 喹啉 、 lithium hydroxide monohydrate 、 氢气 、 copper(I) bromide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 20.0~90.0 ℃ 、101.33 kPa 条件下， 反应 31.0h， 生成 2-((2S,4R)-1-((R,Z)-1-(4-chlorophenyl)-4-methylpent-2-enyl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid
  参考文献：
  名称：

  Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells

  摘要：

  Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimers disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. Compounds named gamma-secretase modulators (GSMs) can shift the substrate cleavage specificity of gamma-secretase toward the production of non-amyloidogenic, shorter A beta fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of gamma-secretase), supporting a mode of action involving binding to gamma-secretase. This fundamental step toward the elucidation of the molecular mechanism governing the GSM-induced shift in gamma-secretase proteolytic specificity should pave the way for the development of improved drugs against AD. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.034