4-氯-N-环己基-N-（苯甲基）苯甲酰胺 | 945714-67-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-N-环己基-N-（苯甲基）苯甲酰胺
• 中文别名: 4-氯-N-环己基-N-(苯基甲基)苯甲酰胺；N-苄基-4-氯-N-环己基苯甲酰胺
• 英文名称: FPS-ZM1
• 英文别名: N-benzyl-4-chloro-N-cyclohexylbenzamide
• CAS: 945714-67-0
• 化学式: C₂₀H₂₂ClNO
• 分子量: 327.854
• InChiKey: XDFKWGIBQMHSOH-UHFFFAOYSA-N

物化性质

• 沸点：
  497.6±38.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（高达35mg/ml）或乙醇（高达20mg/ml）

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

FPS-ZM1是一种能透过血脑屏障、无毒性的三级酰胺化合物，且是RAGE（核因子κB配体受体）的特异性抑制剂，能够有效阻止Aβ与RAGE的V区域结合。

靶点

Target	Value
RAGE

体外研究

FPS-ZM1能有效地阻止Aβ与RAGE的V区域结合，在表达RAGE的细胞中，它还能抑制由Aβ40和Aβ42诱导的细胞应激。此外，它同样能够抑制其他配体如S100B、AGE及HMGB1与RAGE的结合。这些配体可能参与了RAGE介导的长期组织损伤（例如糖尿病模型中）、免疫/炎症疾病以及阿尔茨海默病等。

体内研究

FPS-ZM1对小鼠无毒性，能够通过血脑屏障。在患有Aβ和淀粉样病变的APPSw/0小鼠中，它能有效抑制脑部及血脑屏障中的RAGE，从而控制由Aβ引起的脑部疾病、相关神经血管损害以及认知障碍的发展。

反应信息

• 作为产物：
  描述：

  苯甲醛 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 4-氯-N-环己基-N-（苯甲基）苯甲酰胺
  参考文献：
  名称：

  Structure–activity relationships of small molecule inhibitors of RAGE-Aβ binding

  摘要：

  The Receptor for Advanced Glycation Endproducts ('RAGE') mediates transport of amyloid-beta peptide (A beta) into the brain, and is therefore an important target for the development of therapeutic agents for Alzheimer's disease. We describe structure activity relationships for inhibition of RAGE-A beta binding, derived from the analysis of a library of tertiary amides. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.05.079

文献信息

• Biomarkers for detecting pre-cachexia or cachexia and methods of treatment thereof
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US10191033B2

  公开（公告）日：2019-01-29

  The invention provides markers indicative of pre-cachexia, compositions and methods for identifying patients with a molecular signature indicative of pre-cachexia; a culture system that reproduces the cachetic process in cells in vitro, which facilitates the screening and identification of therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing) the progression of pre-cachexia to refractory cachexia; as well as therapeutic agents identified using the culture system of the invention.

  本发明提供了表明恶病质前期的标记物、用于鉴定具有表明恶病质前期的分子特征的患者的组合物和方法；在体外再现细胞中的恶病质过程的培养系统，该系统有利于筛选和鉴定用于破坏（减缓、减少、逆转或预防）恶病质前期向难治性恶病质进展的治疗剂；以及使用本发明培养系统鉴定的治疗剂。
• Methods for identifying and treating cachexia or pre-cachexia using an inhibitor of rage
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US11058903B2

  公开（公告）日：2021-07-13

  The invention provides markers indicative of pre-cachexia, compositions and methods for identifying patients with a molecular signature indicative of pre-cachexia; a culture system that reproduces the cachetic process in cells in vitro, which facilitates the screening and identification of therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing) the progression of pre-cachexia to refractory cachexia; as well as therapeutic agents identified using the culture system of the invention.

  本发明提供了表明恶病质前期的标记物、用于鉴定具有表明恶病质前期的分子特征的患者的组合物和方法；在体外再现细胞中的恶病质过程的培养系统，该系统有利于筛选和鉴定用于破坏（减缓、减少、逆转或预防）恶病质前期向难治性恶病质进展的治疗剂；以及使用本发明培养系统鉴定的治疗剂。
• ANTIBODIES, COMPOUNDS AND SCREENS FOR IDENTIFYING AND TREATING CACHEXIA OR PRE-CACHEXIA
  申请人：The Broad Institute, Inc.

  公开号：EP3307781B1

  公开（公告）日：2020-10-28
• Inhibiting Amyloid-Beta Peptide/Rage Interaction At The Blood-Brain Barrier
  申请人：Zlokovic Berislav V.

  公开号：US20110039908A1

  公开（公告）日：2011-02-17

  Small molecules are used to inhibit specific receptor-ligand interaction between Alzheimer's amyloid-β peptide (Aβ) and Receptor for Advanced Gly-cation Endproducts (RAGE). Objectives include treating Alzheimer's disease and other pathologies involving cerebral amyloid angiopathy; improving blood flow to or within the brain; decreasing the level of Aβ in the brain; reducing neuropathology associated with Alzheimer's disease; reducing inflammation and/or oxidant stress in the brain; improving memory and/or learning; treating other conditions involving Aβ/RAGE interaction at the blood-brain barrier, RAGE-mediated transport of Aβ into the brain, or RAGE activation in brain vasculature and/or brain parenchyma (e.g., diabetic complications); or any combination thereof.
• S100A8/A9 as a Diagnostic Marker and a Therapeutic Target
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US20150065575A1

  公开（公告）日：2015-03-05

  Determinations of the level of expression of S100A8/A9 protein serve as a prognostic indicator of the therapeutic response to a given type of chemotherapy treatment and as a monitoring indicator of the effectiveness of an on-going chemotherapy treatment for the treatment of breast cancer in human patients. Kits can be used for performing these determinations.