methyl 2-((2S,4R)-1-((S)-1-(4-chlorophenyl)-4-methylpent-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetate | 1404070-13-8

• 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: methyl 2-((2S,4R)-1-((S)-1-(4-chlorophenyl)-4-methylpent-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetate
• 英文别名: methyl 2-[(2S,4R)-1-[(1S)-1-(4-chlorophenyl)-4-methylpent-2-ynyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetate
• CAS: 1404070-13-8
• 化学式: C₂₇H₂₉ClF₃NO₂
• 分子量: 491.981
• InChiKey: ILCMGQUGJHRINW-WVQWTBLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-((2S,4R)-1-((S)-1-(4-chlorophenyl)-4-methylpent-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以80%的产率得到2-((2S,4R)-1-((S)-1-(4-chlorophenyl)-4-methylpent-2-yn-1-yl)-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
• 作为产物：
  描述：

  methyl 2-((2S,4R)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetate 、 3-甲基-1-丁炔 、 4-氯苯甲醛 在 copper(I) bromide 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以40%的产率得到methyl 2-((2S,4R)-1-((S)-1-(4-chlorophenyl)-4-methylpent-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetate
  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

文献信息

• Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells
  作者：Andreas Rennhack、Thorsten Jumpertz、Julia Ness、Sandra Baches、Claus U. Pietrzik、Sascha Weggen、Bruno Bulic

  DOI：10.1016/j.bmc.2012.08.034

  日期：2012.11

  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.