4-[1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester | 1043896-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-[1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
• CAS: 1043896-92-9
• 化学式: C₂₆H₂₅FN₂O₅
• 分子量: 464.493
• InChiKey: ILTKHGJVTJFJEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.84
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-[1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester 在 sodium hydroxide 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.67h， 以87%的产率得到4-[1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
  参考文献：
  名称：

  Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities

  摘要：

  Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

  DOI：

  10.1021/jm8001422
• 作为产物：
  描述：

  3-acetyl-1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4-(1H)-quinolinone 、 草酸二乙酯 在 sodium ethanolate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以82%的产率得到4-[1-(4-fluorophenyl)methyl-7-(pyrrolidin-1-yl)-4(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
  参考文献：
  名称：

  Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities

  摘要：

  Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

  DOI：

  10.1021/jm8001422