N-(ethylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyerane

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(ethylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyerane
• 英文别名: N-[(1R,4S,5R,9S,10R,13S)-5,9,13-trimethyl-14-oxo-5-tetracyclo[11.2.1.01,10.04,9]hexadecanyl]propanamide
• 化学式: C₂₂H₃₅NO₂
• 分子量: 345.525
• InChiKey: HCDADFIPBBLLAR-RHSMJXSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  异甜菊醇 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 水 、 氢溴酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 24.0h， 生成 N-(ethylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyerane
  参考文献：
  名称：

  Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives

  摘要：

  A series of novel isosteviol derivatives having C4-amide substituents were synthesized in order to test for antiviral effects against the hepatitis B virus (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4 alpha-amino- 19-nor-ent-16-ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of its antiviral activity was further analyzed using HBV-transfected Huh7 cells. Exposure to IN-4 produced minimal inhibitory effects on viral precore/pregenomic RNA expression. However, expression levels of the 2.4/2.1-kb preS/major S RNA of the viral surface gene significantly decreased, along with intracellular levels of HBV DNA. A promoter activity analysis demonstrated that IN-4 significantly inhibited viral X, S, and preS expression levels but not viral core promoter activities. In particular, IN-4 was observed to significantly inhibit HBV gene regulation by disrupting nuclear factor (NF)-kappa B-associated promoter activity. In addition, the nuclear expression of p65/p50 NF-kappa B member proteins was attenuated following IN-4 treatment, while cytoplasmic I kappa B alpha protein levels were enhanced. Meanwhile, IN-4 was observed to inhibit the binding activity of NF-kappa B to putative DNA elements. Furthermore, transfection of a p65 expression plasmid into Huh7 cells significantly reversed the inhibitory effect of IN-4 on HBV DNA levels, providing further evidence of the central role of NF-kappa B in its antiviral mechanism. It is therefore suggested that IN-4 inhibits HBV by interfering with the NF-kappa B signaling pathway, resulting in downregulation of viral gene expression and DNA replication. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.064

文献信息

• Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives
  作者：Tsurng-Juhn Huang、Cheng-Lin Yang、Yu-Cheng Kuo、Yi-Chih Chang、Li-Ming Yang、Bo-Hon Chou、Shwu-Jiuan Lin

  DOI：10.1016/j.bmc.2014.12.064

  日期：2015.2

  A series of novel isosteviol derivatives having C4-amide substituents were synthesized in order to test for antiviral effects against the hepatitis B virus (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4 alpha-amino- 19-nor-ent-16-ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of its antiviral activity was further analyzed using HBV-transfected Huh7 cells. Exposure to IN-4 produced minimal inhibitory effects on viral precore/pregenomic RNA expression. However, expression levels of the 2.4/2.1-kb preS/major S RNA of the viral surface gene significantly decreased, along with intracellular levels of HBV DNA. A promoter activity analysis demonstrated that IN-4 significantly inhibited viral X, S, and preS expression levels but not viral core promoter activities. In particular, IN-4 was observed to significantly inhibit HBV gene regulation by disrupting nuclear factor (NF)-kappa B-associated promoter activity. In addition, the nuclear expression of p65/p50 NF-kappa B member proteins was attenuated following IN-4 treatment, while cytoplasmic I kappa B alpha protein levels were enhanced. Meanwhile, IN-4 was observed to inhibit the binding activity of NF-kappa B to putative DNA elements. Furthermore, transfection of a p65 expression plasmid into Huh7 cells significantly reversed the inhibitory effect of IN-4 on HBV DNA levels, providing further evidence of the central role of NF-kappa B in its antiviral mechanism. It is therefore suggested that IN-4 inhibits HBV by interfering with the NF-kappa B signaling pathway, resulting in downregulation of viral gene expression and DNA replication. (c) 2014 Elsevier Ltd. All rights reserved.