phenyl (3,4-dicyanophenyl)carbamate | 117346-10-8

• 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: phenyl (3,4-dicyanophenyl)carbamate
• 英文别名: phenyl N-(3,4-dicyanophenyl)carbamate
• CAS: 117346-10-8
• 化学式: C₁₅H₉N₃O₂
• 分子量: 263.255
• InChiKey: YYNKGVRXTIHNFN-UHFFFAOYSA-N

物化性质

• 沸点：
  449.9±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  85.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1,4-trans)-4-(4-(trifluoromethyl)phenoxy)cyclohexan-1-amine 、 phenyl (3,4-dicyanophenyl)carbamate 在 吡啶 作用下， 反应 3.0h， 以91%的产率得到1-(3,4-dicyanophenyl)-3-((1,4-trans)-4-(4-(trifluoromethyl)phenoxy)cyclohexyl)urea
  参考文献：
  名称：

  Development of 1-((1,4-trans)-4-Aryloxycyclohexyl)-3-arylurea Activators of Heme-Regulated Inhibitor as Selective Activators of the Eukaryotic Initiation Factor 2 Alpha (eIF2α) Phosphorylation Arm of the Integrated Endoplasmic Reticulum Stress Response

  摘要：

  Heme-regulated inhibitor (HRI), an eukaryotic translation initiation factor 2 alpha (eIF2 alpha) kinase, plays critical roles in cell proliferation, differentiation, adaptation to stress, and hemoglobin disorders. HRI phosphorylates eIF2 alpha, which couples cellular signals, including endoplasmic reticulum (ER) stress, to translation. We previously identified 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycydohexyl)-3-arylureas (cHAUs) as specific activators of HRI that trigger the eIF2 alpha phosphorylation arm of ER stress response as molecular probes for studying HRI biology and its potential as a druggable target. To develop drug-like cHAUs needed for in vivo studies, we undertook bioassay-guided structure-activity relationship studies and tested them in the surrogate eIF2 alpha phosphorylation and cell proliferation assays. We further evaluated some of these cHAUs in endogenous eIF2 alpha phosphorylation and in the expression of the transcription factor C/EBP homologous protein (CHOP) and its mRNA, demonstrating significantly improved solubility and/or potencies. These cHAUs are excellent candidates for lead optimization for development of investigational new drugs that potently and specifically activate HRI.

  DOI：

  10.1021/acs.jmedchem.7b00059
• 作为产物：
  描述：

  4-氨基邻苯二甲腈 、 氯甲酸苯酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 phenyl (3,4-dicyanophenyl)carbamate
  参考文献：
  名称：

  Development of 1-((1,4-trans)-4-Aryloxycyclohexyl)-3-arylurea Activators of Heme-Regulated Inhibitor as Selective Activators of the Eukaryotic Initiation Factor 2 Alpha (eIF2α) Phosphorylation Arm of the Integrated Endoplasmic Reticulum Stress Response

  摘要：

  Heme-regulated inhibitor (HRI), an eukaryotic translation initiation factor 2 alpha (eIF2 alpha) kinase, plays critical roles in cell proliferation, differentiation, adaptation to stress, and hemoglobin disorders. HRI phosphorylates eIF2 alpha, which couples cellular signals, including endoplasmic reticulum (ER) stress, to translation. We previously identified 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycydohexyl)-3-arylureas (cHAUs) as specific activators of HRI that trigger the eIF2 alpha phosphorylation arm of ER stress response as molecular probes for studying HRI biology and its potential as a druggable target. To develop drug-like cHAUs needed for in vivo studies, we undertook bioassay-guided structure-activity relationship studies and tested them in the surrogate eIF2 alpha phosphorylation and cell proliferation assays. We further evaluated some of these cHAUs in endogenous eIF2 alpha phosphorylation and in the expression of the transcription factor C/EBP homologous protein (CHOP) and its mRNA, demonstrating significantly improved solubility and/or potencies. These cHAUs are excellent candidates for lead optimization for development of investigational new drugs that potently and specifically activate HRI.

  DOI：

  10.1021/acs.jmedchem.7b00059