prop-2-enyl 7-(chloromethyl)-8-hydroxy-5-oxo-2,4-dihydro-1H-chromeno[3,4-c]pyridine-3-carboxylate | 1607803-40-6

• 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: prop-2-enyl 7-(chloromethyl)-8-hydroxy-5-oxo-2,4-dihydro-1H-chromeno[3,4-c]pyridine-3-carboxylate
• CAS: 1607803-40-6
• 化学式: C₁₇H₁₆ClNO₅
• 分子量: 349.771
• InChiKey: UBYAMESGUWGDHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(allyloxycarbonylamino)propionic acid 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 氯化亚砜 、 乙酸酐 、 N,N'-二异丙基碳二亚胺 作用下， 以 甲醇 、 甲烷磺酸 、 二氯甲烷 、 乙腈 为溶剂， 反应 54.67h， 生成 prop-2-enyl 7-(chloromethyl)-8-hydroxy-5-oxo-2,4-dihydro-1H-chromeno[3,4-c]pyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis of Novel Tricyclic Chromenone-Based Inhibitors of IRE-1 RNase Activity

  摘要：

  Inositol-requiring enzyme 1 (IRE-1) is a kinase/RNase ER stress sensor that is activated in response to excessive accumulation of unfolded proteins, hypoxic conditions, calcium imbalance, and other stress stimuli. Activation of IRE-1 RNase function exerts a cytoprotective effect and has been implicated in the progression of cancer via increased expression of the transcription factor XBP-1s. Here, we describe the synthesis and biological evaluation of novel chromenone-based covalent inhibitors of IRE-1. Preparation of a family of 8-formyltetrahydrochromeno[3,4-c]pyridines was achieved via a Duff formylation that is attended by an unusual cyclization reaction. Biological evaluation in vitro and in whole cells led to the identification of 30 as a potent inhibitor of IRE-1 RNase activity and XBP-1s expression in wild type B cells and human mantle cell lymphoma cell lines.

  DOI：

  10.1021/jm5002452

文献信息

• Synthesis of Novel Tricyclic Chromenone-Based Inhibitors of IRE-1 RNase Activity
  作者：Sujeewa Ranatunga、Chih-Hang Anthony Tang、Chang Won Kang、Crystina L. Kriss、Bernhard J. Kloppenburg、Chih-Chi Andrew Hu、Juan R. Del Valle

  DOI：10.1021/jm5002452

  日期：2014.5.22

  Inositol-requiring enzyme 1 (IRE-1) is a kinase/RNase ER stress sensor that is activated in response to excessive accumulation of unfolded proteins, hypoxic conditions, calcium imbalance, and other stress stimuli. Activation of IRE-1 RNase function exerts a cytoprotective effect and has been implicated in the progression of cancer via increased expression of the transcription factor XBP-1s. Here, we describe the synthesis and biological evaluation of novel chromenone-based covalent inhibitors of IRE-1. Preparation of a family of 8-formyltetrahydrochromeno[3,4-c]pyridines was achieved via a Duff formylation that is attended by an unusual cyclization reaction. Biological evaluation in vitro and in whole cells led to the identification of 30 as a potent inhibitor of IRE-1 RNase activity and XBP-1s expression in wild type B cells and human mantle cell lymphoma cell lines.