1-(4-Chlorophenyl)-3-(2,6-difluorophenyl)prop-2-en-1-one | 1095396-00-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(4-Chlorophenyl)-3-(2,6-difluorophenyl)prop-2-en-1-one
• CAS: 1095396-00-1
• 化学式: C₁₅H₉ClF₂O
• 分子量: 278.686
• InChiKey: IPXUTLOYGPPZFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.07
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  1-(4-Chlorophenyl)-3-(2,6-difluorophenyl)prop-2-en-1-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 cis-5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Triazolo-pyrimidine Derivatives as Novel Inhibitors of Hepatitis B Virus Surface Antigen (HBsAg) Secretion

  摘要：

  The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies. Thus, a therapy that specifically reduces HBsAg serum levels could be used in combination therapy with nucleos(t)ide drugs or permit therapeutic vaccination for the treatment of HBV infection. Herein, we report the design, synthesis, and evaluation of novel triazolo-pyrimidine inhibitors (1, 3, and 4) of HBsAg cellular secretion, with activity against drug-resistant HBV variants. Extensive SAR led to substantial improvements in the EC50 of the parent compound, 5 (HBF-0259), with the best being 3c, with EC50 = 1.4 +/- 0.4 mu M, SI >= 36. The lead candidates, both la (PBHBV-001) and 3c (PBHBV-2-15), were well-tolerated in both normal and HBV-transgenic mice and exhibited acceptable pharmacokinetics and bioavailability in Sprague-Dawley rats.

  DOI：

  10.1021/jm200696v
• 作为产物：
  描述：

  2,6-二氟苯甲醛 、 对氯苯乙酮 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 1-(4-Chlorophenyl)-3-(2,6-difluorophenyl)prop-2-en-1-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Triazolo-pyrimidine Derivatives as Novel Inhibitors of Hepatitis B Virus Surface Antigen (HBsAg) Secretion

  摘要：

  The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies. Thus, a therapy that specifically reduces HBsAg serum levels could be used in combination therapy with nucleos(t)ide drugs or permit therapeutic vaccination for the treatment of HBV infection. Herein, we report the design, synthesis, and evaluation of novel triazolo-pyrimidine inhibitors (1, 3, and 4) of HBsAg cellular secretion, with activity against drug-resistant HBV variants. Extensive SAR led to substantial improvements in the EC50 of the parent compound, 5 (HBF-0259), with the best being 3c, with EC50 = 1.4 +/- 0.4 mu M, SI >= 36. The lead candidates, both la (PBHBV-001) and 3c (PBHBV-2-15), were well-tolerated in both normal and HBV-transgenic mice and exhibited acceptable pharmacokinetics and bioavailability in Sprague-Dawley rats.

  DOI：

  10.1021/jm200696v

文献信息

• Synthesis and in vitro cytotoxicity study of 3-(1H-indol-3-yl)-1,3-diphenylpropan-1-ones
  作者：Jagadeesh N. Masagalli、Kittappa M. Mahadevan、Honnali Jayadevappa、Hosanagara N. Harishkumar、Rajesha Ganalu、Prashantha Nagaraja

  DOI：10.1007/s00044-013-0875-y

  日期：2014.6

  A series of 3-(1H-indol-3-yl)-1,3-diphenylpropan-1-ones 3a-l were synthesized in good to excellent yield by Michael addition of indole 1 with alpha,beta-unsaturated ketones 2a-l in presence of indium(III) sulphate (20 mol%). The structure of the title compounds were established by H-1 NMR, C-13 NMR, mass and elemental analysis. All the synthesized compounds were evaluated for in vitro cytotoxicity against five different cancer cell lines such as ACHN (human kidney adenocarcinoma), Panc1 (pancreatic), Calu1 (lung), H460 (non small cell lung), HCT116 (human colon cancer cell) and MCF10A (normal breast epithelium) using propidium iodide staining assay protocol. The result showed that the compounds 3e and 3l have excellent cytotoxic activity with the IC50 value ranging from 1.4-2.7 to 2.4-3.4 mu M, respectively, in comparison with the other compounds, Flavopiridol and Gemcitabine were employed as a positive control. The findings conferred 3-(1H-indol-3-yl)-1,3-diphenylpropan-1-ones seem to be promising candidates for the development of new anticancer drugs.