N-(4-bromophenyl)-3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-methylbenzamide | 1373116-25-6

• 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-bromophenyl)-3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-methylbenzamide
• 英文别名: N-(4-bromophenyl)-3-[(4-chlorophenyl)-methylsulfamoyl]-N-methylbenzamide
• CAS: 1373116-25-6
• 化学式: C₂₁H₁₈BrClN₂O₃S
• 分子量: 493.809
• InChiKey: UVHNUHDZBJMELO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯-N-甲基苯胺 、 3-氯磺酰基苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-(4-bromophenyl)-3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-methylbenzamide
  参考文献：
  名称：

  3-(N-Arylsulfamoyl)benzamides, inhibitors of human sirtuin type 2 (SIRT2)

  摘要：

  Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl) benzamide(C2-8, 1a), which demonstrated neuroprotective effects in a Huntington's mouse model, but had low potency of SIRT2 inhibition. Here we report that N-methylation of 1a greatly increases its potency and results in excellent selectivity for SIRT2 over SIRT1 and SIRT3 isoforms. Structure-activity relationships observed for 1a analogs and docking simulation data suggest that the para-substituted amido moiety of these compounds could occupy two potential hydrophobic binding pockets in SIRT2. These results provide a direction for the design of potent drug-like SIRT2 inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.089

文献信息

• 3-(N-Arylsulfamoyl)benzamides, inhibitors of human sirtuin type 2 (SIRT2)
  作者：Soo Hyuk Choi、Luisa Quinti、Aleksey G. Kazantsev、Richard B. Silverman

  DOI：10.1016/j.bmcl.2012.02.089

  日期：2012.4

  Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl) benzamide(C2-8, 1a), which demonstrated neuroprotective effects in a Huntington's mouse model, but had low potency of SIRT2 inhibition. Here we report that N-methylation of 1a greatly increases its potency and results in excellent selectivity for SIRT2 over SIRT1 and SIRT3 isoforms. Structure-activity relationships observed for 1a analogs and docking simulation data suggest that the para-substituted amido moiety of these compounds could occupy two potential hydrophobic binding pockets in SIRT2. These results provide a direction for the design of potent drug-like SIRT2 inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.