3-[(2,6-Dichlorophenyl)methyl]-1,3-thiazolidine-2,4-dione

• 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: 3-[(2,6-Dichlorophenyl)methyl]-1,3-thiazolidine-2,4-dione
• 化学式: C₁₀H₇Cl₂NO₂S
• 分子量: 276.143
• InChiKey: JHMFDMQMMCUEPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-chlorophenyl)-2-cyanoacrylate 、 3-[(2,6-Dichlorophenyl)methyl]-1,3-thiazolidine-2,4-dione 生成 5-(4-chlorobenzylidene)-3-(2,6-dichlorobenzyl)thiazolidine-2,4-dione
  参考文献：
  名称：

  New thiazolidinediones affect endothelial cell activation and angiogenesis

  摘要：

  Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists used in treating type 2 diabetes that may exhibit beneficial pleiotropic effects on endothelial cells. In this study, we characterized the effects of three new TZDs [GQ-32 (3-biphenyl-4-ylmethyl 5 (4 nitro benzylidene)thiazolidine-2,4-dione), GQ-169 (5-(4-chloro-benzylidene)-3-(2,6-dichloro-benzyl)-thiazolidine-2,4-dione), and LYSO-7 (5-(5-bromo-1H-indol-3-ylmethylene)-3-(4-chlorobenzyl)-thiazolidine-2,4-dione)] on endothelial cells. The effects of the new TZDs were evaluated on the production of nitric oxide (NO) and reactive oxygen species (ROS), cell migration, tube formation and the gene expression of adhesion molecules and angiogenic mediators in human umbilical vein endothelial cells (HUVECs). PPAR gamma activation by new TZDs was addressed with a reporter gene assay. The three new TZDs activated PPAR gamma and suppressed the tumor necrosis factor alpha-induced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. GQ-169 and LYSO-7 also inhibited the glucose-induced ROS production. Although NO production assessed with 4-amino-5-methylamino-2',7'-difluorofluorescein-FM probe indicated that all tested TZDs enhanced intracellular levels of NO, only LYSO-7 treatment significantly increased the release of NO from HUVEC measured by chemiluminescence analysis of culture media. Additionally, GQ-32 and GQ-169 induced endothelial cell migration and tube formation by the up-regulation of angiogenic molecules expression, such as vascular endothelial growth factor A and interleukin 8. GQ-169 also increased the mRNA levels of basic fibroblast growth factor, and GQ-32 enhanced transforming growth factor-beta expression. Together, the results of this study reveal that these new TZDs act as partial agonists of PPAR gamma and modulate endothelial cell activation and endothelial dysfunction besides to stimulate migration and tube formation. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2016.04.038
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-[(2,6-Dichlorophenyl)methyl]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  New thiazolidinediones affect endothelial cell activation and angiogenesis

  摘要：

  Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists used in treating type 2 diabetes that may exhibit beneficial pleiotropic effects on endothelial cells. In this study, we characterized the effects of three new TZDs [GQ-32 (3-biphenyl-4-ylmethyl 5 (4 nitro benzylidene)thiazolidine-2,4-dione), GQ-169 (5-(4-chloro-benzylidene)-3-(2,6-dichloro-benzyl)-thiazolidine-2,4-dione), and LYSO-7 (5-(5-bromo-1H-indol-3-ylmethylene)-3-(4-chlorobenzyl)-thiazolidine-2,4-dione)] on endothelial cells. The effects of the new TZDs were evaluated on the production of nitric oxide (NO) and reactive oxygen species (ROS), cell migration, tube formation and the gene expression of adhesion molecules and angiogenic mediators in human umbilical vein endothelial cells (HUVECs). PPAR gamma activation by new TZDs was addressed with a reporter gene assay. The three new TZDs activated PPAR gamma and suppressed the tumor necrosis factor alpha-induced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. GQ-169 and LYSO-7 also inhibited the glucose-induced ROS production. Although NO production assessed with 4-amino-5-methylamino-2',7'-difluorofluorescein-FM probe indicated that all tested TZDs enhanced intracellular levels of NO, only LYSO-7 treatment significantly increased the release of NO from HUVEC measured by chemiluminescence analysis of culture media. Additionally, GQ-32 and GQ-169 induced endothelial cell migration and tube formation by the up-regulation of angiogenic molecules expression, such as vascular endothelial growth factor A and interleukin 8. GQ-169 also increased the mRNA levels of basic fibroblast growth factor, and GQ-32 enhanced transforming growth factor-beta expression. Together, the results of this study reveal that these new TZDs act as partial agonists of PPAR gamma and modulate endothelial cell activation and endothelial dysfunction besides to stimulate migration and tube formation. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2016.04.038