3-(2-chloro-6-fluorophenyl)-1-(pyridin-2-yl)prop-2-en-1-one | 1320361-77-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-(2-chloro-6-fluorophenyl)-1-(pyridin-2-yl)prop-2-en-1-one
• CAS: 1320361-77-0
• 化学式: C₁₄H₉ClFNO
• 分子量: 261.683
• InChiKey: MXHMUFYKWJQGMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  18.0
• 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：
  29.96
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(2-chloro-6-fluorophenyl)-1-(pyridin-2-yl)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-7-(2-chloro-6-fluorophenyl)-5-(pyridin-2-yl)-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-乙酰基吡啶 、 2-氯-6-氟-苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 3-(2-chloro-6-fluorophenyl)-1-(pyridin-2-yl)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

• Highly enantioselective synthesis of naphthoquinones and pyranonaphthoquinones catalyzed by bifunctional chiral bis-squaramides
  作者：Nagaraju Molleti、Vinod K. Singh

  DOI：10.1039/c5ob00105f

  日期：——

  bis-squaramide catalyzed conjugate addition of 2-hydroxy-1,4-naphthoquinone to 2-enoylpyridines. Some of the Michael products have been successfully converted into various enantioenriched pyranonaphthoquinone derivatives. The protocol is further extended to the synthesis of various 4-hydroxycoumarin derivatives under mild conditions.

  使用2-羟基-1,4-萘醌双官能手性双-方酸催化的共轭加成反应到2-烯丙基吡啶中，已高收率和优异的对映选择性（高达> 99％ee）合成了多种对映体富集的萘醌。Michael的某些产品已成功转化为各种对映体富集的吡喃并萘醌衍生物。该方案进一步扩展到在温和条件下合成各种4-羟基香豆素衍生物。
• Bifunctional chiral urea catalyzed highly enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to 2-enoylpyridines
  作者：Nagaraju Molleti、Suresh Allu、Sumit K. Ray、Vinod K. Singh

  DOI：10.1016/j.tetlet.2013.04.003

  日期：2013.6

  A highly efficient cinchona alkaloid based bifunctional urea catalyzed enantioselective conjugate addition of cyclic 1,3-dicarbonyl compounds to a range of β-substituted 2-enoylpyridines has been developed. Chiral 2,4-diaryl substituted 1,4-dihydropyridines could easily be accessible from these Michael adducts. Significantly, this asymmetric methodology could afford both enantiomers of the products

  已经开发了一种高效的基于金鸡纳生物碱的双官能脲催化的环状1，3-二羰基化合物对一定范围的β-取代的2-烯丙基吡啶的对映选择性共轭加成。从这些迈克尔加合物容易获得手性的2，4-二芳基取代的1，4-二氢吡啶。重要的是，这种不对称方法可以通过使用具有高达98％ee的假对映异构体催化剂并以极高的收率提供具有相同对映体选择性的两种产品对映体。