N-methylmorpholinium 4-[3-(benzyloxy)phenyl]-3-cyano-6-oxo-1,4,5,6-tetrahydro-pyridine-2-thiolate | 1448816-12-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-methylmorpholinium 4-[3-(benzyloxy)phenyl]-3-cyano-6-oxo-1,4,5,6-tetrahydro-pyridine-2-thiolate
• CAS: 1448816-12-3
• 化学式: C₅H₁₁NO*C₁₉H₁₆N₂O₂S
• 分子量: 437.563
• InChiKey: QGIQFOHFBFCACY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  74.59
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 N-methylmorpholinium 4-[3-(benzyloxy)phenyl]-3-cyano-6-oxo-1,4,5,6-tetrahydro-pyridine-2-thiolate 、 4-乙基苯胺 以 乙醇 、 水 为溶剂， 以51%的产率得到8-[3-(benzyloxy)phenyl]-3-(4-ethylphenyl)-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazine-9-carbonitrile
  参考文献：
  名称：

  Inhibitors of Tick-Borne Flavivirus Reproduction from Structure-Based Virtual Screening

  摘要：

  Flaviviruses form a large family of enveloped viruses affecting millions of people over the world. To date, no specific therapy was suggested for the infected people, making the treatment exclusively symptomatic. Several attempts were performed earlier for the design of fusion inhibitors for mosquito-borne flaviviruses, whereas for the tick-borne flaviviruses such design had not been performed. We have constructed homology models of envelope glycoproteins of tick-transmitted flaviviruses with the detergent binding pocket in the open state. Molecular docking of substituted 1,4-dihydropyridines and pyrido[2,1-b][1,3,5]-thiadiazines was made against these models, and 89 hits were selected for the in vitro experimental evaluation. Seventeen compounds showed significant inhibition against tick-borne encephalitis virus, Powassan virus, or Omsk hemorrhagic fever virus in the 50% plaque reduction test in PEK. cells. These compounds identified through rational design are the first ones possessing reproduction inhibition activity against tick-borne flaviviruses.

  DOI：

  10.1021/ml400226s
• 作为产物：
  描述：

  以 乙醇 为溶剂， 反应 4.0h， 以68%的产率得到N-methylmorpholinium 4-[3-(benzyloxy)phenyl]-3-cyano-6-oxo-1,4,5,6-tetrahydro-pyridine-2-thiolate
  参考文献：
  名称：

  Inhibitors of Tick-Borne Flavivirus Reproduction from Structure-Based Virtual Screening

  摘要：

  Flaviviruses form a large family of enveloped viruses affecting millions of people over the world. To date, no specific therapy was suggested for the infected people, making the treatment exclusively symptomatic. Several attempts were performed earlier for the design of fusion inhibitors for mosquito-borne flaviviruses, whereas for the tick-borne flaviviruses such design had not been performed. We have constructed homology models of envelope glycoproteins of tick-transmitted flaviviruses with the detergent binding pocket in the open state. Molecular docking of substituted 1,4-dihydropyridines and pyrido[2,1-b][1,3,5]-thiadiazines was made against these models, and 89 hits were selected for the in vitro experimental evaluation. Seventeen compounds showed significant inhibition against tick-borne encephalitis virus, Powassan virus, or Omsk hemorrhagic fever virus in the 50% plaque reduction test in PEK. cells. These compounds identified through rational design are the first ones possessing reproduction inhibition activity against tick-borne flaviviruses.

  DOI：

  10.1021/ml400226s

文献信息

• Design and Synthesis of Pyrido[2,1-<i>b</i>][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction
  作者：Victor V. Dotsenko、Konstantin A. Frolov、Tatyana M. Pekhtereva、Olena S. Papaianina、Sergey Yu. Suykov、Sergey G. Krivokolysko

  DOI：10.1021/co5000807

  日期：2014.10.13

  This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.