3-(1-methyl-1H-indol-3-yl)-1-pentyl-4-(propylamino)-1H-pyrrole-2,5-dione

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(1-methyl-1H-indol-3-yl)-1-pentyl-4-(propylamino)-1H-pyrrole-2,5-dione
• 英文别名: 3-(1-Methylindol-3-yl)-1-pentyl-4-(propylamino)pyrrole-2,5-dione；3-(1-methylindol-3-yl)-1-pentyl-4-(propylamino)pyrrole-2,5-dione
• 化学式: C₂₁H₂₇N₃O₂
• 分子量: 353.464
• InChiKey: ZXZQSELKHBATMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 3-(1-methyl-1H-indol-3-yl)-1-pentyl-4-(propylamino)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Development of a Water-Soluble Indolylmaleimide Derivative IM-93 Showing Dual Inhibition of Ferroptosis and NETosis

  摘要：

  The indolylmaleimide (IM) derivative IM-17 shows inhibitory activity against oxidative-stress-induced necrotic cell death and cardioprotective activity in rat ischemia-reperfusion injury models. In order to develop a more potent derivative, we conducted a detailed structure-activity relationship study of IM derivatives and identified IM 93 as the most potent derivative with good water solubility. IM-93 inhibited ferroptosis and NETosis, but not necroptosis or pyroptosis. In contrast, ferrostatin-1 (Fer-1), a ferroptosis inhibitor, did not inhibit NETosis, although the accompanying lipid peroxidation was partially inhibited by Fer-1, as well as by IM-93. Thus, IM derivatives have a unique activity profile and appear to be promising candidates for in vivo application.

  DOI：

  10.1021/acsmedchemlett.9b00142

文献信息

• Development of a Water-Soluble Indolylmaleimide Derivative IM-93 Showing Dual Inhibition of Ferroptosis and NETosis
  作者：Kosuke Dodo、Erika Kuboki、Tadashi Shimizu、Ryu Imamura、Megumi Magarisawa、Masahiro Takahashi、Takuto Tokuhiro、Satoshi Yotsumoto、Kenichi Asano、Shuhei Nakao、Naoki Terayama、Takashi Suda、Masato Tanaka、Mikiko Sodeoka

  DOI：10.1021/acsmedchemlett.9b00142

  日期：2019.9.12

  The indolylmaleimide (IM) derivative IM-17 shows inhibitory activity against oxidative-stress-induced necrotic cell death and cardioprotective activity in rat ischemia-reperfusion injury models. In order to develop a more potent derivative, we conducted a detailed structure-activity relationship study of IM derivatives and identified IM 93 as the most potent derivative with good water solubility. IM-93 inhibited ferroptosis and NETosis, but not necroptosis or pyroptosis. In contrast, ferrostatin-1 (Fer-1), a ferroptosis inhibitor, did not inhibit NETosis, although the accompanying lipid peroxidation was partially inhibited by Fer-1, as well as by IM-93. Thus, IM derivatives have a unique activity profile and appear to be promising candidates for in vivo application.