(E)-6-[1-[(4-fluorophenyl)methyl]-4-phenyl-pyrrol-3-yl]-2,4-dioxo-hex-5-enoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (E)-6-[1-[(4-fluorophenyl)methyl]-4-phenyl-pyrrol-3-yl]-2,4-dioxo-hex-5-enoic acid
• 英文别名: (E)-6-[1-[(4-fluorophenyl)methyl]-4-phenylpyrrol-3-yl]-2,4-dioxohex-5-enoic acid
• 化学式: C₂₃H₁₈FNO₄
• 分子量: 391.399
• InChiKey: RLHCTBNHVKIBTQ-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E,E)-6-phenyl-3,5-hexadien-2-one 在 sodium hydroxide 、 sodium ethanolate 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.33h， 生成 (E)-6-[1-[(4-fluorophenyl)methyl]-4-phenyl-pyrrol-3-yl]-2,4-dioxo-hex-5-enoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of heteroaryl diketohexenoic and diketobutanoic acids as HIV-1 integrase inhibitors endowed with antiretroviral activity

  摘要：

  Highly active anti-retroviral therapy (HAART) using reverse transcriptase (RT) and protease (PR) inhibitors and, more recently, inhibitors of the fusion is currently the best clinical approach in combating acquired immunodeficiency syndrome (AIDS), caused by infection from human immunodeficiency virus type 1 (HIV-1). However, this therapy does not completely eradicate the virus, so that resistant strains easily emerge. The above problem calls urgently for research on inhibitors of further viral targets such as integrase (IN), the third enzyme produced by HIV. Recently, our research group was engaged in studies on conformationally restrained cinnamoyl compounds related to curcumin as anti-IN agents. Compounds containing both a 3,4,5-trihydroxyphenyl group and a carboxylic acid function were potent IN inhibitors active against viral replication. More recently, a promising new class of inhibitors synthesized by Merck Company has emerged, which contain aryldiketoacid (ADK) functionality. The ADKs selectively inhibited the stand transfer (ST) step of integration and were proven to be effective IN inhibitors in vivo. Our interest in the field of IN inhibitors led us to design pyrrole and indole derivatives containing both a cinnamoyl moiety and a diketoacid group. A number of the cited derivatives were proven potent IN inhibitors, which selectively inhibited the ST step at submicromolar concentrations and were effective against virus replication in HIV-1 infected cells.

  DOI：

  10.1016/j.farmac.2005.03.008