4-(5-chlorosalicyloyl)-1-phenylpiperazine | 1088148-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(5-chlorosalicyloyl)-1-phenylpiperazine
• 英文别名: (5-Chloro-2-hydroxyphenyl)-(4-phenylpiperazin-1-yl)methanone
• CAS: 1088148-56-4
• 化学式: C₁₇H₁₇ClN₂O₂
• 分子量: 316.787
• InChiKey: RKABGORHUIOZTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 在 硫酸 作用下， 以 甲醇 为溶剂， 反应 37.0h， 生成 4-(5-chlorosalicyloyl)-1-phenylpiperazine
  参考文献：
  名称：

  Structure–activity relationship of salicylic acid derivatives on inhibition of TNF-α dependent NFκB activity: Implication on anti-inflammatory effect of N-(5-chlorosalicyloyl)phenethylamine against experimental colitis

  摘要：

  To develop a more potent NF kappa B inhibitor from salicylic acid which is known to inhibit activity of NF kappa B, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NF kappa B dependent luciferase gene and LPS-stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of chlorine at the 5 position increased the ability of SA to suppress the expression of NF kappa B dependent luciferase and inducible nitric oxide synthase, a product of an NF kappa B target gene. Moreover, simultaneous amidation and chlorination of SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NF kappa B inhibitory activity on SA. To further enhance the inhibitory activity. N-modification was imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5-chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4-hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting NF kappa B activity than other derivatives. Their IC(50)s' in the luciferase assay measured 15 mu M (5-CSPA), 17 mu M (5-CSPPA) and 91 mu M (5-CSHPA). Rectal administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more effective than a conventional drug, 5-aminosalicylic acid. These data may provide useful information for development of a therapeutic agent for treatment of diseases where NF kappa B plays a critical role in the pathogenic progresses. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.030

文献信息

• Structure–activity relationship of salicylic acid derivatives on inhibition of TNF-α dependent NFκB activity: Implication on anti-inflammatory effect of N-(5-chlorosalicyloyl)phenethylamine against experimental colitis
  作者：Jihye Kim、Sookjin Kang、Sungchae Hong、Soowhan Yum、Young Mi Kim、Yunjin Jung

  DOI：10.1016/j.ejmech.2011.11.030

  日期：2012.2

  To develop a more potent NF kappa B inhibitor from salicylic acid which is known to inhibit activity of NF kappa B, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NF kappa B dependent luciferase gene and LPS-stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of chlorine at the 5 position increased the ability of SA to suppress the expression of NF kappa B dependent luciferase and inducible nitric oxide synthase, a product of an NF kappa B target gene. Moreover, simultaneous amidation and chlorination of SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NF kappa B inhibitory activity on SA. To further enhance the inhibitory activity. N-modification was imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5-chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4-hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting NF kappa B activity than other derivatives. Their IC(50)s' in the luciferase assay measured 15 mu M (5-CSPA), 17 mu M (5-CSPPA) and 91 mu M (5-CSHPA). Rectal administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more effective than a conventional drug, 5-aminosalicylic acid. These data may provide useful information for development of a therapeutic agent for treatment of diseases where NF kappa B plays a critical role in the pathogenic progresses. (C) 2011 Elsevier Masson SAS. All rights reserved.