N'-(4-chlorophenyl)-N-[3-(4-chlorophenyl)-1-(2-hydrazino-2-oxoethyl)-5,5-dimethyl-2-oxo-4-imidazolidinyl]-N-hydroxyurea | 318272-53-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: N'-(4-chlorophenyl)-N-[3-(4-chlorophenyl)-1-(2-hydrazino-2-oxoethyl)-5,5-dimethyl-2-oxo-4-imidazolidinyl]-N-hydroxyurea
• 英文别名: 3-(4-chlorophenyl)-1-[3-(4-chlorophenyl)-1-(2-hydrazinyl-2-oxoethyl)-5,5-dimethyl-2-oxoimidazolidin-4-yl]-1-hydroxyurea
• CAS: 318272-53-6
• 化学式: C₂₀H₂₂Cl₂N₆O₄
• 分子量: 481.338
• InChiKey: QYKFNOGIBJQLKF-UHFFFAOYSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  反-3-(2-呋喃基)丙烯醛 、 N'-(4-chlorophenyl)-N-[3-(4-chlorophenyl)-1-(2-hydrazino-2-oxoethyl)-5,5-dimethyl-2-oxo-4-imidazolidinyl]-N-hydroxyurea 反应 48.0h， 生成 N’-(4-Chlorophenyl)-N-[3-(4-chlorophenyl)-2-oxo-1-(2-{2-[3-(2-furyl)-2-propen-1-ylidene]hydrazino}-2-oxoethyl)-5,5-dimethyl-4-imidazolidinyl]-N-hydroxyurea
  参考文献：
  名称：

  Eeyarestatin Compounds Selectively Enhance Sec61-Mediated Ca2+ Leakage from the Endoplasmic Reticulum

  摘要：

  Eeyarestatin 1 (ES1) inhibits p97-dependent protein degradation, Sec61-dependent protein translocation into the endoplasmic reticulum (ER), and vesicular transport within the endomembrane system. Here, we show that ES1 impairs Ca2+ homeostasis by enhancing the Ca2+ leakage from mammalian ER. A comparison of various ES1 analogs suggested that the 5-nitrofuran (5-NF) ring of ES1 is crucial for this effect. Accordingly, the analog ES24, which conserves the 5-NF domain of ES1, selectively inhibited protein translocation into the ER, displayed the highest potency on ER Ca2+ leakage of ES1 analogs studied and induced Ca2+-dependent cell death. Using small interfering RNA-mediated knockdown of Sec61 alpha, we identified Sec61 complexes as the targets that mediate the gain of Ca2+ leakage induced by ES1 and ES24. By interacting with the lateral gate of Sec61 alpha, ES1 and ES24 likely capture Sec61 complexes in a Ca2+-permeable, open state, in which Sec61 complexes allow Ca2+ leakage but are translocation incompetent.

  DOI：

  10.1016/j.chembiol.2019.01.010

文献信息

• HYDRAZONE AND DIACYL HYDRAZINE COMPOUNDS AND METHODS OF USE
  申请人：Wiestner Adrian

  公开号：US20120316198A1

  公开（公告）日：2012-12-13

  Disclosed herein are novel hydrazone and diacyl hydrazine derivatives that are inhibitors of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Also disclosed are hydrazone and diacyl hydrazine derivatives as potent and selective inhibitors of the p97 ATPase. These agents provide useful tools for the study of protein degradation and other processes involving p97. Methods of treating diseases or disorders for which p97 inhibition and/or ER stress induction is an effective treatment with certain hydrazone and diacyl hydrazine derivatives are also disclosed.

  本文披露了一种新型的腙和二酰基肼衍生物，它们是内质网相关蛋白降解（ERAD）途径的抑制剂。还披露了腙和二酰基肼衍生物作为p97 ATP酶的有效和选择性抑制剂。这些药剂为研究蛋白降解和其他涉及p97的过程提供了有用的工具。还披露了使用某些腙和二酰基肼衍生物治疗p97抑制和/或ER应激诱导是有效治疗某些疾病或疾病的方法。
• US8518968B2
  申请人：——

  公开号：US8518968B2

  公开（公告）日：2013-08-27