ent-16-oxobeyeran-19-N-methylureido | 1569100-89-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: ent-16-oxobeyeran-19-N-methylureido
• 英文别名: NC-8；1-methyl-3-[(1R,4S,5R,9S,10R,13S)-5,9,13-trimethyl-14-oxo-5-tetracyclo[11.2.1.01,10.04,9]hexadecanyl]urea
• CAS: 1569100-89-5
• 化学式: C₂₁H₃₄N₂O₂
• 分子量: 346.513
• InChiKey: YAAZCYZLITZGTA-XNRDYXSJSA-N

物化性质

• 沸点：
  514.2±39.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4α-isocyanato-19-nor-ent-16-ketobeyeran 、 甲胺 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到ent-16-oxobeyeran-19-N-methylureido
  参考文献：
  名称：

  Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus

  摘要：

  Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N-methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in HepG2 2.2.15 cells. Its anti-HBV mechanism was then next investigated in a human hepatoma cell culture system. Results showed that it specifically inhibited viral gene expression and reduced the level of encapsidated viral DNA intermediates in Huh7 cells that expressed replicating HBV. It also potently attenuated all viral promoter activity in HBV-expressing Huh7 cells, but not in cells lacking HBV expression. By examining its antiviral mechanism in cellular signaling pathways, NC-8 was found to inhibit the activity of the nuclear factor (NF)-kappa B element-containing promoter, but only slightly enhanced activities of activator protein (AP)-1-and interferon-sensitive response element (ISRE)-containing promoters in HBV-expressing cells. NC-8 also significantly eliminated NE-kappa B (p65/p50) and Toll-like receptor (TLR)2 proteins, but increased the I kappa B alpha protein level in a dose-dependent manner in HBV-transfected Huh7 cells, while these protein levels were apparently unchanged in non-transfected cells. Meanwhile, NC-8-treated nuclear extracts that co-expressed HBV inhibited the binding of NF-kappa B to the CSI site of HBV major surface gene and specifically attenuated CS1-containing promoter activity. Taken together, this study suggests that the antiviral mechanism of NC-8 appears to be mediated by disturbing replication and gene expression of HBV and by inhibiting the host TLR2/NF-kappa B signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.phytochem.2013.12.014

文献信息

• Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus
  作者：Tsurng-Juhn Huang、Bo-Hon Chou、Cheng-Wen Lin、Jen-Hsien Weng、Chang-Hung Chou、Li-Ming Yang、Shwu-Jiuan Lin

  DOI：10.1016/j.phytochem.2013.12.014

  日期：2014.3

  Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N-methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in HepG2 2.2.15 cells. Its anti-HBV mechanism was then next investigated in a human hepatoma cell culture system. Results showed that it specifically inhibited viral gene expression and reduced the level of encapsidated viral DNA intermediates in Huh7 cells that expressed replicating HBV. It also potently attenuated all viral promoter activity in HBV-expressing Huh7 cells, but not in cells lacking HBV expression. By examining its antiviral mechanism in cellular signaling pathways, NC-8 was found to inhibit the activity of the nuclear factor (NF)-kappa B element-containing promoter, but only slightly enhanced activities of activator protein (AP)-1-and interferon-sensitive response element (ISRE)-containing promoters in HBV-expressing cells. NC-8 also significantly eliminated NE-kappa B (p65/p50) and Toll-like receptor (TLR)2 proteins, but increased the I kappa B alpha protein level in a dose-dependent manner in HBV-transfected Huh7 cells, while these protein levels were apparently unchanged in non-transfected cells. Meanwhile, NC-8-treated nuclear extracts that co-expressed HBV inhibited the binding of NF-kappa B to the CSI site of HBV major surface gene and specifically attenuated CS1-containing promoter activity. Taken together, this study suggests that the antiviral mechanism of NC-8 appears to be mediated by disturbing replication and gene expression of HBV and by inhibiting the host TLR2/NF-kappa B signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved.