2,6-dichloro-N-[2-(3-cyanobenzylsulfanyl)ethyl]benzamide | 1234380-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,6-dichloro-N-[2-(3-cyanobenzylsulfanyl)ethyl]benzamide
• 英文别名: 2,6-Dichloro-N-[2-(3-cyano-benzylsulfanyl)-ethyl]-benzamide；2,6-dichloro-N-[2-[(3-cyanophenyl)methylsulfanyl]ethyl]benzamide
• CAS: 1234380-61-0
• 化学式: C₁₇H₁₄Cl₂N₂OS
• 分子量: 365.283
• InChiKey: VXMHZQXJVOEEKY-UHFFFAOYSA-N

物化性质

• 熔点：
  123 °C
• 沸点：
  528.7±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-N-[2-(3-cyanobenzylsulfanyl)ethyl]benzamide 在 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以42%的产率得到2,6-dichloro-N-(2-[3-(N'-hydroxycarbamimidoyl)-benzylsulfanyl]-ethyl)-benzamide
  参考文献：
  名称：

  COMPOSITIONS AND METHODS FOR INHIBITING BETA AMYLOID SECRETION

  摘要：

  一种用于抑制受体内淀粉样蛋白β的药物组合物包括具有以下式(I)的化合物： 其中M从取代或未取代的烷基、卤素、烷氧基、芳基、环状或杂环基中选择； p是0-3之间的整数； X1是一个连接A和B的长度为3-9个原子的连接物； B从取代或未取代的芳基、烷氧基或胺基中选择；以及其药学上可接受的盐；和药用载体。

  公开号：

  US20130158112A1
• 作为产物：
  描述：

  3-(2-Amino-ethylsulfanylmethyl)-benzonitrile 、 2,6-二氯苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2,6-dichloro-N-[2-(3-cyanobenzylsulfanyl)ethyl]benzamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Analogues of a Novel Inhibitor of β-Amyloid Secretion

  摘要：

  A drug library of 17200 compounds was screened to select small molecules that inhibit the secretion of amyloid beta peptide (Am, the major component of Alzheimer disease senile plaques, from a human neuronal cell line. Twenty-nine hits were validated that decreased A beta secretion by >40% at 10 mu M, for a 0.17% hit rate. A lead hit was selected for further study based on its activity and low cytotoxicity, and it was found to inhibit A beta secretion through activation of the alpha-secretase pathway. Twenty-four commercially available and 53 synthesized analogues were analyzed for activity. Selected analogues were evaluated for biological stability by incubation with hepatoma cells and for transcellular permeability using Caco-2 cell monolayers. The analogue with the best permeability was evaluated in 2-month old amyloid precursor protein transgenic mice and found to acutely reduce cerebral A beta levels by 40% after a single iv administration.

  DOI：

  10.1021/jm100308g

文献信息

• COMPOSITIONS AND METHODS FOR INHIBITING BETA AMYLOID SECRETION
  申请人：Smith Jonathan D.

  公开号：US20130158112A1

  公开（公告）日：2013-06-20

  A pharmaceutical composition for inhibiting amyloid beta peptide in a subject includes a compound having the formula (I): where M is selected from a substituted or unsubstituted alkyl, halo, alkoxy, aryl, cyclic, or heterocyclic group; p is an integer from 0-3; X 1 is a 3-9 atoms in length linker connecting A and B; B is selected from a substituted or unsubstituted aryl, alkoxy or amine group; and a pharmaceutically acceptable salt thereof; and a pharmaceutical carrier.

  一种用于抑制受体内淀粉样蛋白β的药物组合物包括具有以下式(I)的化合物： 其中M从取代或未取代的烷基、卤素、烷氧基、芳基、环状或杂环基中选择； p是0-3之间的整数； X1是一个连接A和B的长度为3-9个原子的连接物； B从取代或未取代的芳基、烷氧基或胺基中选择；以及其药学上可接受的盐；和药用载体。
• Synthesis and Biological Evaluation of Analogues of a Novel Inhibitor of β-Amyloid Secretion
  作者：Enakshi Chakrabarti、Subrata Ghosh、Sushabhan Sadhukhan、Lawrence Sayre、Gregory P. Tochtrop、Jonathan D. Smith

  DOI：10.1021/jm100308g

  日期：2010.7.22

  A drug library of 17200 compounds was screened to select small molecules that inhibit the secretion of amyloid beta peptide (Am, the major component of Alzheimer disease senile plaques, from a human neuronal cell line. Twenty-nine hits were validated that decreased A beta secretion by >40% at 10 mu M, for a 0.17% hit rate. A lead hit was selected for further study based on its activity and low cytotoxicity, and it was found to inhibit A beta secretion through activation of the alpha-secretase pathway. Twenty-four commercially available and 53 synthesized analogues were analyzed for activity. Selected analogues were evaluated for biological stability by incubation with hepatoma cells and for transcellular permeability using Caco-2 cell monolayers. The analogue with the best permeability was evaluated in 2-month old amyloid precursor protein transgenic mice and found to acutely reduce cerebral A beta levels by 40% after a single iv administration.