1,12-bis-{3-[1-(benzyl)ureado]}-4,9-[N-(tert-butyl)oxycarbonyl]-4,9-diazadodecane | 1234495-15-8

• 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: 1,12-bis-{3-[1-(benzyl)ureado]}-4,9-[N-(tert-butyl)oxycarbonyl]-4,9-diazadodecane
• 英文别名: tert-butyl N-[3-(benzylcarbamoylamino)propyl]-N-[4-[3-(benzylcarbamoylamino)propyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl]carbamate
• CAS: 1234495-15-8
• 化学式: C₃₆H₅₆N₆O₆
• 分子量: 668.877
• InChiKey: BHZXRIOFGLABEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  48
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,12-bis-{3-[1-(benzyl)ureado]}-4,9-[N-(tert-butyl)oxycarbonyl]-4,9-diazadodecane 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 48.0h， 以94%的产率得到1,12-bis-{3-[1-(benzyl)ureado]}-4,9-diazadodecane dihydrochloride
  参考文献：
  名称：

  (Bis)urea and (Bis)thiourea Inhibitors of Lysine-Specific Demethylase 1 as Epigenetic Modulators

  摘要：

  The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and.transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.

  DOI：

  10.1021/jm100217a
• 作为产物：
  描述：

  异氰酸苄酯 、 di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) 以 二氯甲烷 为溶剂， 反应 24.0h， 以86%的产率得到1,12-bis-{3-[1-(benzyl)ureado]}-4,9-[N-(tert-butyl)oxycarbonyl]-4,9-diazadodecane
  参考文献：
  名称：

  [EN] (BIS) UREA AND (BIS) THIOUREA COMPOUNDS AS EPIGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS
  [FR] COMPOSÉS (BIS)URÉE ET (BIS)THIOURÉE EN TANT QUE MODULATEURS ÉPIGÉNIQUES DE LA DÉMÉTHYLASE 1 SPÉCIFIQUE À LA LYSINE ET MÉTHODES DE TRAITEMENT DE TROUBLES

  摘要：

  公开号：

  WO2011022489A3

文献信息

• [EN] (BIS) UREA AND (BIS) THIOUREA COMPOUNDS AS EPIGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS<br/>[FR] COMPOSÉS (BIS)URÉE ET (BIS)THIOURÉE EN TANT QUE MODULATEURS ÉPIGÉNIQUES DE LA DÉMÉTHYLASE 1 SPÉCIFIQUE À LA LYSINE ET MÉTHODES DE TRAITEMENT DE TROUBLES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2011022489A3

  公开（公告）日：2011-06-16
• (Bis)urea and (Bis)thiourea Inhibitors of Lysine-Specific Demethylase 1 as Epigenetic Modulators
  作者：Shiv K. Sharma、Yu Wu、Nora Steinbergs、Michael L. Crowley、Allison S. Hanson、Robert A. Casero、Patrick M. Woster

  DOI：10.1021/jm100217a

  日期：2010.7.22

  The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and.transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.