5-amino-3-dodecyl-9-methyl-1H-chromeno[3,4-c]pyridine-2,4(3H,10bH)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-amino-3-dodecyl-9-methyl-1H-chromeno[3,4-c]pyridine-2,4(3H,10bH)-dione
• 英文别名: 5-amino-3-dodecyl-9-methyl-1,10b-dihydrochromeno[3,4-c]pyridine-2,4-dione
• 化学式: C₂₅H₃₆N₂O₃
• 分子量: 412.572
• InChiKey: ZLUMDCLPHBNDJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-十二烷基-2-氰基乙酰胺 、 6-甲基香豆素 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 5-amino-3-dodecyl-9-methyl-1H-chromeno[3,4-c]pyridine-2,4(3H,10bH)-dione
  参考文献：
  名称：

  Discovery of chromenes as inhibitors of macrophage migration inhibitory factor

  摘要：

  Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aim to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tautomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50's in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.032

文献信息

• Discovery of chromenes as inhibitors of macrophage migration inhibitory factor
  作者：Tjie Kok、Hannah Wapenaar、Kan Wang、Constantinos G. Neochoritis、Tryfon Zarganes-Tzitzikas、Giordano Proietti、Nikolaos Eleftheriadis、Katarzyna Kurpiewska、Justyna Kalinowska-Tłuścik、Robbert H. Cool、Gerrit J. Poelarends、Alexander Dömling、Frank J. Dekker

  DOI：10.1016/j.bmc.2017.12.032

  日期：2018.3

  Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aim to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tautomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50's in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved. (C) 2017 Elsevier Ltd. All rights reserved.