(Z)-5-((1H-indol-3-yl)methylene)-2-p-tolylthiazol-4(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (Z)-5-((1H-indol-3-yl)methylene)-2-p-tolylthiazol-4(5H)-one
• 英文别名: (5Z)-5-(1H-indol-3-ylmethylidene)-2-(4-methylphenyl)-1,3-thiazol-4-one
• 化学式: C₁₉H₁₄N₂OS
• 分子量: 318.399
• InChiKey: KSDKHWQGRAPYGV-YVLHZVERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  45.22
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  3-吲哚甲醛 、 巯基乙酸 、 对甲苯腈 在 三乙胺 作用下， 反应 0.25h， 以7%的产率得到(Z)-5-((1H-indol-3-yl)methylene)-2-p-tolylthiazol-4(5H)-one
  参考文献：
  名称：

  Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

  摘要：

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.054

文献信息

• Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy
  作者：Andreas P. Lill、Carmen B. Rödl、Dieter Steinhilber、Holger Stark、Bettina Hofmann

  DOI：10.1016/j.ejmech.2014.10.054

  日期：2015.1

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.