2-[1-Benzyl-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetic acid | 1404070-23-0

• 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-[1-Benzyl-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetic acid
• CAS: 1404070-23-0
• 化学式: C₂₁H₂₂F₃NO₂
• 分子量: 377.406
• InChiKey: VQQVXAYLJZWUMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[1-Benzyl-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetic acid 在 4-二甲氨基吡啶 、 10% Pd/C 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 copper(I) bromide 作用下， 以 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 49.17h， 生成
  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：

  溴甲苯 在 lithium hydroxide monohydrate 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 0.25h， 生成 2-[1-Benzyl-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

文献信息

• Piperidines and Related Compounds for Treatment of Alzheimer's Disease
  申请人：Hannam Clare Joanne

  公开号：US20080021043A1

  公开（公告）日：2008-01-24

  Compounds of formula I: selectively inhibit production of Aβ(1-42) and hence are useful in treatment or prevention of disease associated with deposition of β-amyloid in the brain.

  化学式为I的化合物：选择性地抑制Aβ（1-42）的产生，因此在治疗或预防与β-淀粉样蛋白在大脑中沉积相关的疾病方面是有用的。
• PIPERIDINES AND RELATED COMPOUNDS FOR TREATMENT OF ALZHEIMER'S DISEASE
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1805141B1

  公开（公告）日：2010-01-20
• US7638629B2
  申请人：——

  公开号：US7638629B2

  公开（公告）日：2009-12-29
• [EN] PIPERIDINES AND RELATED COMPOUNDS FOR TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] PIPÉRIDINES ET COMPOSÉS APPARENTÉS POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK SHARP & DOHME

  公开号：WO2006043064A1

  公开（公告）日：2006-04-27

  [EN] Compounds of formula (I), selectively inhibit production of Aß (1-42) and hence are useful in treatment or prevention of disease assocaited with deposition of ß -amyloid in the brain.
  [FR] La présente invention décrit des composés de formule (I) qui inhibent de façon sélective la production de Aß (1-42), et peuvent donc être employés dans le traitement prophylactique ou thérapeutique de maladies associées au dépôt de ß-amyloïde dans le cerveau.