4-(4-Phenylpiperazin-1-yl)sulfonylbenzoic acid

• 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-(4-Phenylpiperazin-1-yl)sulfonylbenzoic acid
• 化学式: C₁₇H₁₈N₂O₄S
• 分子量: 346.407
• InChiKey: QAJQMBUVGXDFNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苯基哌嗪 、 4-(氯磺酰)苯甲酸 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 4-(4-Phenylpiperazin-1-yl)sulfonylbenzoic acid
  参考文献：
  名称：

  Synthesis and pharmacological characterization of benzenesulfonamides as dual species inhibitors of human and murine mPGES-1

  摘要：

  The microsomal prostaglandin E-2 synthase 1 (mPGES-1) became a desirable target in recent years for the research of new anti-inflammatory drugs. Even though many potent inhibitors of human mPGES-1, tested in vitro assay systems, have been synthesized, they all failed in preclinical trials in rodent models of inflammation, due to the lack of activity on rodent enzyme. Within this work we want to present a new class of mPGES-1 inhibitors derived from a benzenesulfonamide scaffold with inhibitory potency on human and murine mPGES-1. Starting point with an IC50 of 13.8 mu M on human mPGES-1 was compound 1 (4-{benzyl[(4-methoxyphenyl) methyl] sulfamoyl} benzoic acid; FR4), which was discovered by a virtual screening approach. Optimization during a structure-activity relationship (SAR) process leads to compound 28 (4-[(cyclohexylmethyl)[(4-phenylphenyl) methyl] sulfamoyl] benzoic acid) with an improved IC50 of 0.8 mu M on human mPGES-1. For the most promising compounds a broad pharmacological characterization has been carried out to estimate their anti-inflammatory potential. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.006