N-phenyl-N'-(2-methoxyphenoxycarbonyl)-4-methylphenylsulfonhydrazide

• 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-phenyl-N'-(2-methoxyphenoxycarbonyl)-4-methylphenylsulfonhydrazide
• 英文别名: (2-methoxyphenyl) N-anilino-N-(4-methylphenyl)sulfonylcarbamate
• 化学式: C₂₁H₂₀N₂O₅S
• 分子量: 412.466
• InChiKey: RXEDKUYJNGCQJE-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：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  93.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  苯肼 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-phenyl-N'-(2-methoxyphenoxycarbonyl)-4-methylphenylsulfonhydrazide
  参考文献：
  名称：

  Hit-to-lead optimization of phenylsulfonyl hydrazides for a potent suppressor of PGE2 production: Synthesis, biological activity, and molecular docking study

  摘要：

  Preliminary hit-to-lead optimization of a novel series of phenylsulfonyl hydrazide derivatives, which were derived from the high throughput screening hit compound 1 (IC50 = 5700 nM against PGE(2) production), for a potent suppressor of PGE(2) production is described. Subsequent optimization led to the identification of the potent lead compound 8n with IC50 values of 4.5 and 6.9 nM, respectively, against LPS-induced PGE(2) production and NO production in RAW 264.7 macrophage cells. In addition, 8n was about 30- and > 150-fold more potent against mPGES-1 enzyme in a cell-free assay (IC50 = 70 nM) than MK-886 and hit compound 1, respectively. Molecular docking suggests that compound 8n could inhibit PGE2 production by blocking the PGH(2) binding site of human mPGES-1 enzyme. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.024

文献信息

• Hit-to-lead optimization of phenylsulfonyl hydrazides for a potent suppressor of PGE2 production: Synthesis, biological activity, and molecular docking study
  作者：Minju Kim、Sunhoe Lee、Eun Beul Park、Kwang Jong Kim、Hwi Ho Lee、Ji-Sun Shin、Katrin Fischer、Andreas Koeberle、Oliver Werz、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2015.11.024

  日期：2016.1

  Preliminary hit-to-lead optimization of a novel series of phenylsulfonyl hydrazide derivatives, which were derived from the high throughput screening hit compound 1 (IC50 = 5700 nM against PGE(2) production), for a potent suppressor of PGE(2) production is described. Subsequent optimization led to the identification of the potent lead compound 8n with IC50 values of 4.5 and 6.9 nM, respectively, against LPS-induced PGE(2) production and NO production in RAW 264.7 macrophage cells. In addition, 8n was about 30- and > 150-fold more potent against mPGES-1 enzyme in a cell-free assay (IC50 = 70 nM) than MK-886 and hit compound 1, respectively. Molecular docking suggests that compound 8n could inhibit PGE2 production by blocking the PGH(2) binding site of human mPGES-1 enzyme. (C) 2015 Elsevier Ltd. All rights reserved.