3-(5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one | 1402740-28-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 3-(5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 3-[5-(4-Fluorophenyl)-1,3,4-thiadiazol-2-yl]pyrido[1,2-a]pyrimidin-4-one；3-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]pyrido[1,2-a]pyrimidin-4-one
• CAS: 1402740-28-6
• 化学式: C₁₆H₉FN₄OS
• 分子量: 324.338
• InChiKey: AQDXMIDPRXAOBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbohydrazide 在 劳森试剂 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 3-(5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular modeling studies of new 1,3,4-oxadiazole- and 1,3,4-thiadiazole-substituted 4-oxo-4H-pyrido[1,2-a]pyrimidines as anti-HIV-1 agents

  摘要：

  A new series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives containing 1,3,4-oxadiazole and 1,3,4-thiadiazole rings as a part of the metal chelation motif were synthesized and evaluated for their in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate inhibitory properties against HIV-1 virus (NL4-3) in Hela cell cultures. Compounds 11e and 11b exhibited the highest activity among the synthesized compounds with inhibition rate of 51 and 48 % at concentration of 100 mu M, respectively. Molecular docking study using the later crystallographic data available for PFV integrase (IN) showed that the designed compounds bind into the active site of IN such that the keto oxygen atom at position of C-4 and nitrogen atom of thiadiazole or oxadiazole ring moiety chelate the Mg2+ ion. Our results also showed that all tested compounds presented no significant cytotoxicity at concentration of 100 mu M. Therefore, these compounds can provide a very good basis for the development of new hits.

  DOI：

  10.1007/s00044-012-0241-5

文献信息

• Synthesis, biological evaluation, and molecular modeling studies of new 1,3,4-oxadiazole- and 1,3,4-thiadiazole-substituted 4-oxo-4H-pyrido[1,2-a]pyrimidines as anti-HIV-1 agents
  作者：Z. Hajimahdi、A. Zarghi、R. Zabihollahi、M. R. Aghasadeghi

  DOI：10.1007/s00044-012-0241-5

  日期：2013.5

  A new series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives containing 1,3,4-oxadiazole and 1,3,4-thiadiazole rings as a part of the metal chelation motif were synthesized and evaluated for their in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate inhibitory properties against HIV-1 virus (NL4-3) in Hela cell cultures. Compounds 11e and 11b exhibited the highest activity among the synthesized compounds with inhibition rate of 51 and 48 % at concentration of 100 mu M, respectively. Molecular docking study using the later crystallographic data available for PFV integrase (IN) showed that the designed compounds bind into the active site of IN such that the keto oxygen atom at position of C-4 and nitrogen atom of thiadiazole or oxadiazole ring moiety chelate the Mg2+ ion. Our results also showed that all tested compounds presented no significant cytotoxicity at concentration of 100 mu M. Therefore, these compounds can provide a very good basis for the development of new hits.