N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide

• 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: N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
• 英文别名: N-[(4-fluorophenyl)methyl]-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide
• 化学式: C₂₃H₂₃FN₂O₄S
• 分子量: 442.511
• InChiKey: SYKVYECTCDWLMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  sodium p-hydroxybenzenesulfonate 在 吡啶 、 氯化亚砜 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 12.0h， 生成 N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
  参考文献：
  名称：

  Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors

  摘要：

  Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 mu M in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 mu M in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.060

文献信息

• Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors
  作者：Ya-li Li、Xiang-yu Qi、Hui Jiang、Xiao-dong Deng、Yan-ping Dong、Ting-bo Ding、Lu Zhou、Peng Men、Yong Chu、Ren-xiao Wang、Xian-cheng Jiang、De-yong Ye

  DOI：10.1016/j.bmc.2015.07.060

  日期：2015.9

  Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 mu M in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 mu M in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.